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GeneBe

1-63571026-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_032437.4(EFCAB7):c.1713T>G(p.Asp571Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,601,954 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 47 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 61 hom. )

Consequence

EFCAB7
NM_032437.4 missense

Scores

18

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.597
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]
ITGB3BP (HGNC:6157): (integrin subunit beta 3 binding protein) This gene encodes a transcriptional coregulator that binds to and enhances the activity of members of the nuclear receptor families, thyroid hormone receptors and retinoid X receptors. This protein also acts as a corepressor of NF-kappaB-dependent signaling. This protein induces apoptosis in breast cancer cells through a caspase 2-mediated signaling pathway. This protein is also a component of the centromere-specific histone H3 variant nucleosome associated complex (CENP-NAC) and may be involved in mitotic progression by recruiting the histone H3 variant CENP-A to the centromere. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.0016108751).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-63571026-T-G is Benign according to our data. Variant chr1-63571026-T-G is described in ClinVar as [Benign]. Clinvar id is 720987.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2196/152292) while in subpopulation AFR AF= 0.0504 (2094/41560). AF 95% confidence interval is 0.0486. There are 47 homozygotes in gnomad4. There are 1051 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 47 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EFCAB7NM_032437.4 linkuse as main transcriptc.1713T>G p.Asp571Glu missense_variant 13/14 ENST00000371088.5
EFCAB7XM_006710976.4 linkuse as main transcriptc.1752T>G p.Asp584Glu missense_variant 13/14
EFCAB7XM_006710977.2 linkuse as main transcriptc.1713T>G p.Asp571Glu missense_variant 13/14
EFCAB7XM_011542301.3 linkuse as main transcriptc.1752T>G p.Asp584Glu missense_variant 13/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EFCAB7ENST00000371088.5 linkuse as main transcriptc.1713T>G p.Asp571Glu missense_variant 13/141 NM_032437.4 P1A8K855-1
EFCAB7ENST00000460678.6 linkuse as main transcriptn.995T>G non_coding_transcript_exon_variant 7/75
EFCAB7ENST00000461039.1 linkuse as main transcriptn.3441T>G non_coding_transcript_exon_variant 4/52
ITGB3BPENST00000478138.1 linkuse as main transcriptn.197+22499A>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0144
AC:
2189
AN:
152174
Hom.:
47
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0504
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00465
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00388
AC:
941
AN:
242638
Hom.:
25
AF XY:
0.00293
AC XY:
383
AN XY:
130880
show subpopulations
Gnomad AFR exome
AF:
0.0514
Gnomad AMR exome
AF:
0.00255
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000717
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000180
Gnomad OTH exome
AF:
0.00152
GnomAD4 exome
AF:
0.00150
AC:
2175
AN:
1449662
Hom.:
61
Cov.:
28
AF XY:
0.00131
AC XY:
946
AN XY:
721062
show subpopulations
Gnomad4 AFR exome
AF:
0.0519
Gnomad4 AMR exome
AF:
0.00301
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000143
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000832
Gnomad4 OTH exome
AF:
0.00352
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0144
AC:
2196
AN:
152292
Hom.:
47
Cov.:
32
AF XY:
0.0141
AC XY:
1051
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0504
Gnomad4 AMR
AF:
0.00464
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00246
Hom.:
11
Bravo
AF:
0.0164
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.0461
AC:
203
ESP6500EA
AF:
0.000116
AC:
1
ExAC
?
    Exome Aggregation Consortium database
AF:
0.00475
AC:
576
Asia WGS
AF:
0.00376
AC:
13
AN:
3472

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 25, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.67
Cadd
Benign
13
Dann
Benign
0.91
DEOGEN2
Benign
0.00062
T
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.74
T
MetaRNN
Benign
0.0016
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.63
N
REVEL
Benign
0.22
Sift
Benign
0.35
T
Sift4G
Benign
0.39
T
Polyphen
0.0
B
Vest4
0.12
MutPred
0.21
Gain of solvent accessibility (P = 0.0638);
MVP
0.30
MPC
0.15
ClinPred
0.0080
T
GERP RS
-4.4
Varity_R
0.082
gMVP
0.059

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

LitVar

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

Other links and lift over

dbSNP: rs74568205; hg19: chr1-64036697; API