1-46692814-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014774.3(EFCAB14):c.580-877G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,132 control chromosomes in the GnomAD database, including 2,668 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2668 hom., cov: 32)
• Consequence: EFCAB14 NM_014774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

EFCAB14 (HGNC:29051): (EF-hand calcium binding domain 14) Predicted to enable calcium ion binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFCAB14	NM_014774.3	c.580-877G>A		intron_variant		ENST00000371933.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFCAB14	ENST00000371933.8	c.580-877G>A		intron_variant		1	NM_014774.3	P2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25947 AN: 152014 Hom.: 2666 Cov.: 32

Gnomad AFR AF: 0.0732

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0882

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.170 AC: 25932 AN: 152132 Hom.: 2668 Cov.: 32 AF XY: 0.169 AC XY: 12568 AN XY: 74348

Gnomad4 AFR AF: 0.0730

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.0878

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.159

Alfa AF: 0.111 Hom.: 216

Bravo AF: 0.157

Asia WGS AF: 0.176 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.28
Dann	Benign	0.24

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

Other links and lift over

dbSNP: rs4660956; hg19: chr1-47158486;