dbSNP rs582883: MACF1:c.12939-162T>C (chr1-39369868-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001394062.1(MACF1):c.12939-162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,076 control chromosomes in the GnomAD database, including 11,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 11150 hom., cov: 32)

Consequence

MACF1
NM_001394062.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.232

Publications

10 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 1-39369868-T-C is Benign according to our data. Variant chr1-39369868-T-C is described in ClinVar as Benign. ClinVar VariationId is 1257453.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACF1	NM_001394062.1 link	c.12939-162T>C		intron_variant	Intron 50 of 100	ENST00000564288.6	NP_001380991.1
MACF1	NM_012090.5 link	c.6753-162T>C		intron_variant	Intron 44 of 92		NP_036222.3	Q9UPN3-2Q6ZSD7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACF1	ENST00000564288.6 link	c.12939-162T>C		intron_variant	Intron 50 of 100	5	NM_001394062.1	ENSP00000455274.1		H3BPE1

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55448

AN:

151958

Hom.:

11116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.541

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.352

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.365

AC:

55532

AN:

152076

Hom.:

11150

Cov.:

AF XY:

0.359

AC XY:

26710

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.541

AC:

22454

AN:

41470

American (AMR)

AF:

0.308

AC:

4711

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

1049

AN:

3470

East Asian (EAS)

AF:

0.416

AC:

2147

AN:

5160

South Asian (SAS)

AF:

0.220

AC:

1062

AN:

4822

European-Finnish (FIN)

AF:

0.259

AC:

2745

AN:

10584

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.299

AC:

20344

AN:

67984

Other (OTH)

AF:

0.358

AC:

754

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1760

3520

5280

7040

8800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.310

Hom.:

4594

Bravo

AF:

0.379

Asia WGS

AF:

0.372

AC:

1293

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 13, 2021

GeneDx

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

-0.94

CADD

Benign

2.4

(source)

DANN

Benign

0.27

PhyloP100

-0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over