Variant 1-63561706-CAG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032437.4(EFCAB7):c.1350_1351delGA(p.Asn451fs) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,571,682 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

EFCAB7
NM_032437.4 frameshift, splice_region

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.06

Variant links:

Genes affected

EFCAB7 (HGNC:29379): (EF-hand calcium binding domain 7) Predicted to enable calcium ion binding activity. Predicted to be involved in positive regulation of protein import into nucleus; positive regulation of protein localization to ciliary membrane; and positive regulation of transcription by RNA polymerase II. Predicted to be located in ciliary membrane. Predicted to be extrinsic component of membrane. Predicted to be part of plasma membrane protein complex. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB7 links:

EFCAB7 (HGNC:):

EFCAB7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB7	NM_032437.4 linkuse as main transcript	c.1350_1351delGA	p.Asn451fs	frameshift_variant, splice_region_variant	11/14	ENST00000371088.5	NP_115813.2	A8K855-1
EFCAB7	XM_006710976.4 linkuse as main transcript	c.1389_1390delGA	p.Asn464fs	frameshift_variant, splice_region_variant	11/14		XP_006711039.1
EFCAB7	XM_006710977.2 linkuse as main transcript	c.1350_1351delGA	p.Asn451fs	frameshift_variant, splice_region_variant	11/14		XP_006711040.1	A8K855-1
EFCAB7	XM_011542301.3 linkuse as main transcript	c.1389_1390delGA	p.Asn464fs	frameshift_variant, splice_region_variant	11/14		XP_011540603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EFCAB7	ENST00000371088.5 linkuse as main transcript	c.1350_1351delGA	p.Asn451fs	frameshift_variant, splice_region_variant	11/14	1	NM_032437.4	ENSP00000360129.4	A8K855-1
EFCAB7	ENST00000460678.6 linkuse as main transcript	n.632_633delGA		splice_region_variant, non_coding_transcript_exon_variant	5/7	5
EFCAB7	ENST00000461039.1 linkuse as main transcript	n.577_578delGA		splice_region_variant, non_coding_transcript_exon_variant	3/5	2
ITGB3BP	ENST00000478138.1 linkuse as main transcript	n.197+31817_197+31818delCT		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000711

AC:

AN:

224900

Hom.:

AF XY:

0.0000984

AC XY:

AN XY:

121938

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000802

Gnomad FIN exome

AF:

0.0000480

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000282

AC:

AN:

1419648

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

705122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000386

Gnomad4 FIN exome

AF:

0.0000385

Gnomad4 NFE exome

AF:

0.0000320

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Postaxial polydactyly

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Center for Statistical Genetics, Columbia University

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

1.0

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.96

Position offset: 5

DS_AL_spliceai

1.0

Position offset: 3

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