17-47361422-C-T

Variant names:

• chr17-47361422-C-T
• rs78865644
• NM_152347.5:c.706C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_152347.5(EFCAB13):​c.706C>T​(p.Arg236*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00952 in 1,613,472 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0077 (6 hom., cov: 31)
  • Exomes 𝑓: 0.0097 (84 hom.)
• Consequence: EFCAB13 NM_152347.5 stop_gained
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.50

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 17-47361422-C-T is Benign according to our data. Variant chr17-47361422-C-T is described in ClinVar as [Benign]. Clinvar id is 3041441.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB13	NM_152347.5	c.706C>T	p.Arg236*	stop_gained	Exon 10 of 25	ENST00000331493.7	NP_689560.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB13	ENST00000331493.7	c.706C>T	p.Arg236*	stop_gained	Exon 10 of 25	1	NM_152347.5	ENSP00000332111.2
EFCAB13	ENST00000517484.5	c.518-9015C>T		intron_variant	Intron 8 of 21	2		ENSP00000430048.1
EFCAB13	ENST00000517310.5	c.74-9015C>T		intron_variant	Intron 9 of 10	2		ENSP00000466136.1
EFCAB13	ENST00000520776.5	n.696C>T		non_coding_transcript_exon_variant	Exon 7 of 14	2

Frequencies

GnomAD3 genomes AF: 0.00774 AC: 1177 AN: 151976 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00625

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0206

GnomAD3 exomes AF: 0.00791 AC: 1987 AN: 251326 Hom.: 14 AF XY: 0.00837 AC XY: 1137 AN XY: 135852

Gnomad AFR exome AF: 0.00178

Gnomad AMR exome AF: 0.00813

Gnomad ASJ exome AF: 0.0150

Gnomad EAS exome AF: 0.000598

Gnomad SAS exome AF: 0.00114

Gnomad FIN exome AF: 0.00615

Gnomad NFE exome AF: 0.0114

Gnomad OTH exome AF: 0.00766

GnomAD4 exome AF: 0.00970 AC: 14178 AN: 1461378 Hom.: 84 Cov.: 30 AF XY: 0.00958 AC XY: 6961 AN XY: 726988

Gnomad4 AFR exome AF: 0.00179

Gnomad4 AMR exome AF: 0.00834

Gnomad4 ASJ exome AF: 0.0136

Gnomad4 EAS exome AF: 0.000278

Gnomad4 SAS exome AF: 0.00122

Gnomad4 FIN exome AF: 0.00588

Gnomad4 NFE exome AF: 0.0111

Gnomad4 OTH exome AF: 0.00883

GnomAD4 genome AF: 0.00775 AC: 1178 AN: 152094 Hom.: 6 Cov.: 31 AF XY: 0.00738 AC XY: 549 AN XY: 74354

Gnomad4 AFR AF: 0.00190

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00625

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0102 Hom.: 19

Bravo AF: 0.00830

TwinsUK AF: 0.00809 AC: 30

ALSPAC AF: 0.0122 AC: 47

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.00988 AC: 85

ExAC AF: 0.00772 AC: 937

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EFCAB13-related disorder Benign:1

Feb 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Benign	0.18
Eigen_PC	Benign	-0.069
FATHMM_MKL	Benign	0.46	N
Vest4		0.15
GERP RS		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs78865644; hg19: chr17-45438788; COSMIC: COSV58949015;