1-39447679-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001394062.1(MACF1):c.19762-13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,613,926 control chromosomes in the GnomAD database, including 33,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2431 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30649 hom. )

Consequence

MACF1
NM_001394062.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.713

Publications

29 publications found

Variant links:

Genes affected

MACF1 (HGNC:13664): (microtubule actin crosslinking factor 1) This gene encodes a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. The encoded protein is a member of a family of proteins that form bridges between different cytoskeletal elements. This protein facilitates actin-microtubule interactions at the cell periphery and couples the microtubule network to cellular junctions. Alternative splicing results in multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, May 2013]

MACF1 Gene-Disease associations (from GenCC):

lissencephaly 9 with complex brainstem malformation
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics
lissencephaly spectrum disorder with complex brainstem malformation
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

MACF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-39447679-A-G is Benign according to our data. Variant chr1-39447679-A-G is described in ClinVar as [Benign]. Clinvar id is 1178452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MACF1	NM_001394062.1 link	c.19762-13A>G	intron_variant	Intron 81 of 100	ENST00000564288.6	NP_001380991.1
MACF1	NM_012090.5 link	c.13585-13A>G	intron_variant	Intron 76 of 92		NP_036222.3	Q9UPN3-2Q6ZSD7
MACF1	NM_001397473.1 link	c.7840-13A>G	intron_variant	Intron 24 of 40		NP_001384402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACF1	ENST00000564288.6 link	c.19762-13A>G		intron_variant	Intron 81 of 100	5	NM_001394062.1	ENSP00000455274.1		H3BPE1

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24367

AN:

152070

Hom.:

2430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0408

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.176

GnomAD2 exomes

AF:

0.189

AC:

47344

AN:

250542

AF XY:

0.187

show subpopulations

Gnomad AFR exome

AF:

0.0380

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.204

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.200

AC:

292877

AN:

1461738

Hom.:

30649

Cov.:

AF XY:

0.198

AC XY:

144125

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.0342

AC:

1145

AN:

33480

American (AMR)

AF:

0.217

AC:

9683

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

6142

AN:

26136

East Asian (EAS)

AF:

0.167

AC:

6638

AN:

39700

South Asian (SAS)

AF:

0.113

AC:

9707

AN:

86248

European-Finnish (FIN)

AF:

0.197

AC:

10502

AN:

53414

Middle Eastern (MID)

AF:

0.156

AC:

900

AN:

5768

European-Non Finnish (NFE)

AF:

0.213

AC:

237010

AN:

1111878

Other (OTH)

AF:

0.185

AC:

11150

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

14296

28592

42888

57184

71480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7970

15940

23910

31880

39850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.160

AC:

24364

AN:

152188

Hom.:

2431

Cov.:

AF XY:

0.158

AC XY:

11724

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0408

AC:

1697

AN:

41556

American (AMR)

AF:

0.188

AC:

2867

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

788

AN:

3472

East Asian (EAS)

AF:

0.175

AC:

909

AN:

5182

South Asian (SAS)

AF:

0.107

AC:

518

AN:

4820

European-Finnish (FIN)

AF:

0.205

AC:

2166

AN:

10574

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14894

AN:

67996

Other (OTH)

AF:

0.175

AC:

369

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1029

2058

3087

4116

5145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.202

Hom.:

5774

Bravo

AF:

0.156

Asia WGS

AF:

0.120

AC:

414

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lissencephaly 9 with complex brainstem malformation

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.074

(source)

DANN

Benign

0.38

PhyloP100

-0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over