chr1-46711146-T-C

Variant names:

• chr1-46711146-T-C
• rs2218189
• NM_014774.3:c.335-3095A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EFCAB14	NM_014774.3	c.335-3095A>G		intron_variant	Intron 2 of 10	ENST00000371933.8	NP_055589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB14	ENST00000371933.8	c.335-3095A>G		intron_variant	Intron 2 of 10	1	NM_014774.3	ENSP00000361001.3

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

African (AFR) AF: 0.504 AC: 20909 AN: 41450

American (AMR) AF: 0.410 AC: 6272 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1260 AN: 3472

East Asian (EAS) AF: 0.744 AC: 3851 AN: 5178

South Asian (SAS) AF: 0.383 AC: 1846 AN: 4822

European-Finnish (FIN) AF: 0.258 AC: 2736 AN: 10606

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18230 AN: 67986

Other (OTH) AF: 0.388 AC: 821 AN: 2116

Alfa AF: 0.294 Hom.: 3410

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
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2218189; hg19: chr1-47176818;