1-63557139-G-A

Position:

• chr1-63557139-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032437.4(EFCAB7):​c.1240G>A​(p.Val414Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EFCAB7 NM_032437.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.994

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.021152616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB7	NM_032437.4	c.1240G>A	p.Val414Ile	missense_variant	10/14	ENST00000371088.5	NP_115813.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB7	ENST00000371088.5	c.1240G>A	p.Val414Ile	missense_variant	10/14	1	NM_032437.4	ENSP00000360129.4
EFCAB7	ENST00000460678.6	n.522G>A		non_coding_transcript_exon_variant	4/7	5
EFCAB7	ENST00000461039.1	n.467G>A		non_coding_transcript_exon_variant	2/5	2
ITGB3BP	ENST00000478138.1	n.198-27953C>T		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.1240G>A (p.V414I) alteration is located in exon 10 (coding exon 9) of the EFCAB7 gene. This alteration results from a G to A substitution at nucleotide position 1240, causing the valine (V) at amino acid position 414 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.69
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.13	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.062
Sift	Benign	0.62	T
Sift4G	Benign	0.87	T
Polyphen		0.0010	B
Vest4		0.035
MutPred		0.15		Gain of sheet (P = 0.0827);
MVP		0.25
MPC		0.13
ClinPred		0.15	T
GERP RS		-1.7
Varity_R		0.028
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs1647041122; hg19: chr1-64022810;