1-46689619-C-G

Variant names:

• chr1-46689619-C-G
• rs200564580
• NM_014774.3:c.763G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_014774.3(EFCAB14):​c.763G>C​(p.Asp255His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: EFCAB14 NM_014774.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22
• Publications: 3 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2912805).

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.763G>C	p.Asp255His	missense	Exon 6 of 11	NP_055589.1	O75071
	EFCAB14-AS1	NR_038827.1		n.360-2255C>G		intron	N/A
	EFCAB14-AS1	NR_038828.1		n.276-2255C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB14	ENST00000371933.8	TSL:1 MANE Select	c.763G>C	p.Asp255His	missense	Exon 6 of 11	ENSP00000361001.3	O75071
	EFCAB14	ENST00000672422.2		c.856G>C	p.Asp286His	missense	Exon 6 of 11	ENSP00000499873.2	A0A804H3B5
	EFCAB14	ENST00000674263.1		c.763G>C	p.Asp255His	missense	Exon 6 of 12	ENSP00000501323.1	A0A6I8PIF8

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251266 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000109 AC: 160 AN: 1461558 Hom.: 0 Cov.: 30 AF XY: 0.000110 AC XY: 80 AN XY: 727084

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.000141 AC: 157 AN: 1111780

Other (OTH) AF: 0.0000166 AC: 1 AN: 60376

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000164 Hom.: 0

Bravo AF: 0.0000529

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.29	T
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.093	T
Polyphen		1.0	D
Vest4		0.17
MVP		0.86
MPC		0.63
ClinPred		0.32	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.24
gMVP		0.14
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs200564580; hg19: chr1-47155291;