rs2218189

Positions:

• chr1-46711146-T-C

Variant summary

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

The NM_014774.3(EFCAB14):​c.335-3095A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,118 control chromosomes in the GnomAD database, including 11,626 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 0.37 (11626 hom., cov: 33)
• Consequence: EFCAB14 NM_014774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFCAB14	NM_014774.3	c.335-3095A>G		intron_variant		ENST00000371933.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFCAB14	ENST00000371933.8	c.335-3095A>G		intron_variant		1	NM_014774.3	P2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56128 AN: 152000 Hom.: 11574 Cov.: 33

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.370 AC: 56242 AN: 152118 Hom.: 11626 Cov.: 33 AF XY: 0.376 AC XY: 27934 AN XY: 74386

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.388

Alfa AF: 0.295 Hom.: 3096

Bravo AF: 0.386

Asia WGS AF: 0.563 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.80

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: rs2218189; hg19: chr1-47176818;