Variant rs2296173 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

MACF1 (HGNC:):

MACF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	MANE	Protein	UniProt
MACF1	NM_001394062.1 linkuse as main transcript	c.19762-13A>G	intron_variant	ENST00000564288.6	NP_001380991.1
MACF1	NM_012090.5 linkuse as main transcript	c.13585-13A>G	intron_variant		NP_036222.3	Q9UPN3-2Q6ZSD7
MACF1	NM_001397473.1 linkuse as main transcript	c.7840-13A>G	intron_variant		NP_001384402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACF1	ENST00000564288.6 linkuse as main transcript	c.19762-13A>G		intron_variant		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

GnomAD3 exomes

AF:

0.189

AC:

47344

AN:

250542

Hom.:

4847

AF XY:

0.187

AC XY:

25332

AN XY:

135756

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 SAS exome

AF:

0.109

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

Gnomad4 AFR exome

AF:

0.0342

Gnomad4 AMR exome

AF:

0.217

Gnomad4 ASJ exome

AF:

0.235

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.113

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.213

Gnomad4 OTH exome

AF:

0.185

GnomAD4 genome

AF:

0.160

AC:

24364

AN:

152188

Hom.:

2431

Cov.:

AF XY:

0.158

AC XY:

11724

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0408

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.227

Gnomad4 EAS

AF:

0.175

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.205

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.207

Hom.:

4780

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Lissencephaly 9 with complex brainstem malformation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.074

DANN

Benign

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over