chr17-47361479-C-T

Variant names:

• chr17-47361479-C-T
• rs115917803
• NM_152347.5:c.763C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152347.5(EFCAB13):​c.763C>T​(p.Arg255Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 1,612,222 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: EFCAB13 NM_152347.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 0.138
• Publications: 1 publications found

Genes affected

EFCAB13 (HGNC:26864): (EF-hand calcium binding domain 13)

EFCAB13-DT (HGNC:55338): (EFCAB13 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005517155).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152347.5. 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
	EFCAB13	NM_152347.5	MANE Select	c.763C>T	p.Arg255Cys	missense	Exon 10 of 25	NP_689560.3
	EFCAB13	NM_001426585.1		c.763C>T	p.Arg255Cys	missense	Exon 9 of 23	NP_001413514.1
	EFCAB13	NM_001426586.1		c.619C>T	p.Arg207Cys	missense	Exon 9 of 23	NP_001413515.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB13	ENST00000331493.7	TSL:1 MANE Select	c.763C>T	p.Arg255Cys	missense	Exon 10 of 25	ENSP00000332111.2	Q8IY85-1
	EFCAB13	ENST00000517484.5	TSL:2	c.518-8958C>T		intron	N/A	ENSP00000430048.1	Q8IY85-2
	EFCAB13	ENST00000517310.5	TSL:2	c.74-8958C>T		intron	N/A	ENSP00000466136.1	K7ELL9

Frequencies

GnomAD3 genomes AF: 0.00222 AC: 337 AN: 151810 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00751

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000681 AC: 171 AN: 251046 AF XY: 0.000604

Gnomad AFR exome AF: 0.00881

Gnomad AMR exome AF: 0.000782

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000215 AC: 314 AN: 1460294 Hom.: 0 Cov.: 30 AF XY: 0.000219 AC XY: 159 AN XY: 726458

African (AFR) AF: 0.00736 AC: 246 AN: 33410

American (AMR) AF: 0.000671 AC: 30 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39616

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1110906

Other (OTH) AF: 0.000431 AC: 26 AN: 60322

GnomAD4 genome AF: 0.00222 AC: 337 AN: 151928 Hom.: 1 Cov.: 31 AF XY: 0.00211 AC XY: 157 AN XY: 74246

African (AFR) AF: 0.00749 AC: 310 AN: 41378

American (AMR) AF: 0.00138 AC: 21 AN: 15270

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67954

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.00275

ESP6500AA AF: 0.00908 AC: 40

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000848 AC: 103

EpiCase AF: 0.0000547

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	EFCAB13-related disorder (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.00077	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.14
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.083
Sift	Benign	0.046	D
Sift4G	Uncertain	0.010	D
Polyphen		0.38	B
Vest4		0.27
MVP		0.12
MPC		0.28
ClinPred		0.0055	T
GERP RS		2.8
Varity_R		0.11
gMVP		0.089
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs115917803; hg19: chr17-45438845;