rs2275380

Variant names:

• chr1-46682056-C-T
• rs2275380
• NM_014774.3:c.1312+1244G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014774.3(EFCAB14):​c.1312+1244G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,996 control chromosomes in the GnomAD database, including 12,560 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 0.38 (12560 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: EFCAB14 NM_014774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• 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]

EFCAB14-AS1 (HGNC:44108): (EFCAB14 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014774.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB14	NM_014774.3	MANE Select	c.1312+1244G>A		intron	N/A	NP_055589.1	O75071
	EFCAB14-AS1	NR_038827.1		n.185-125C>T		intron	N/A
	EFCAB14-AS1	NR_038828.1		n.185-4617C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB14	ENST00000371933.8	TSL:1 MANE Select	c.1312+1244G>A		intron	N/A	ENSP00000361001.3	O75071
	EFCAB14	ENST00000672422.2		c.1405+1244G>A		intron	N/A	ENSP00000499873.2	A0A804H3B5
	EFCAB14	ENST00000674263.1		c.1312+1244G>A		intron	N/A	ENSP00000501323.1	A0A6I8PIF8

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57639 AN: 151882 Hom.: 12564 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.379 AC: 57628 AN: 151994 Hom.: 12560 Cov.: 32 AF XY: 0.376 AC XY: 27935 AN XY: 74304

African (AFR) AF: 0.170 AC: 7052 AN: 41460

American (AMR) AF: 0.407 AC: 6219 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1436 AN: 3472

East Asian (EAS) AF: 0.134 AC: 693 AN: 5186

South Asian (SAS) AF: 0.320 AC: 1546 AN: 4830

European-Finnish (FIN) AF: 0.482 AC: 5067 AN: 10518

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.503 AC: 34197 AN: 67942

Other (OTH) AF: 0.395 AC: 831 AN: 2106

Alfa AF: 0.464 Hom.: 11029

Bravo AF: 0.365

Asia WGS AF: 0.210 AC: 733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.59
PhyloP100		-0.45
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: rs2275380; hg19: chr1-47147728;