17-47347921-C-T

Variant names:

• chr17-47347921-C-T
• rs71377306
• NM_152347.5:c.631C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PP3 BP6 BA1

The NM_152347.5(EFCAB13):​c.631C>T​(p.Arg211*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,529,114 control chromosomes in the GnomAD database, including 3,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.052 (389 hom., cov: 30)
  • Exomes 𝑓: 0.061 (3509 hom.)
• Consequence: EFCAB13 NM_152347.5 stop_gained
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.06
• Publications: 18 publications found

Genes affected

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

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 17-47347921-C-T is Benign according to our data. Variant chr17-47347921-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059359.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

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.631C>T	p.Arg211*	stop_gained	Exon 9 of 25	NP_689560.3
	EFCAB13	NM_001426585.1		c.631C>T	p.Arg211*	stop_gained	Exon 8 of 23	NP_001413514.1
	EFCAB13	NM_001426587.1		c.631C>T	p.Arg211*	stop_gained	Exon 9 of 23	NP_001413516.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB13	ENST00000331493.7	TSL:1 MANE Select	c.631C>T	p.Arg211*	stop_gained	Exon 9 of 25	ENSP00000332111.2	Q8IY85-1
	EFCAB13	ENST00000517484.5	TSL:2	c.517+2823C>T		intron	N/A	ENSP00000430048.1	Q8IY85-2
	EFCAB13	ENST00000517310.5	TSL:2	c.73+2823C>T		intron	N/A	ENSP00000466136.1	K7ELL9

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7896 AN: 151978 Hom.: 389 Cov.: 30

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0524

Gnomad OTH AF: 0.0569

GnomAD2 exomes AF: 0.0737 AC: 17721 AN: 240478 AF XY: 0.0763

Gnomad AFR exome AF: 0.00901

Gnomad AMR exome AF: 0.0227

Gnomad ASJ exome AF: 0.0392

Gnomad EAS exome AF: 0.241

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0564

Gnomad OTH exome AF: 0.0677

GnomAD4 exome AF: 0.0609 AC: 83832 AN: 1377018 Hom.: 3509 Cov.: 31 AF XY: 0.0623 AC XY: 42140 AN XY: 676276

African (AFR) AF: 0.00934 AC: 302 AN: 32332

American (AMR) AF: 0.0245 AC: 1022 AN: 41650

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 974 AN: 24484

East Asian (EAS) AF: 0.222 AC: 8467 AN: 38136

South Asian (SAS) AF: 0.113 AC: 7979 AN: 70678

European-Finnish (FIN) AF: 0.110 AC: 5596 AN: 50924

Middle Eastern (MID) AF: 0.0626 AC: 342 AN: 5462

European-Non Finnish (NFE) AF: 0.0522 AC: 55207 AN: 1056970

Other (OTH) AF: 0.0699 AC: 3943 AN: 56382

GnomAD4 genome AF: 0.0518 AC: 7884 AN: 152096 Hom.: 389 Cov.: 30 AF XY: 0.0558 AC XY: 4146 AN XY: 74330

African (AFR) AF: 0.0109 AC: 454 AN: 41494

American (AMR) AF: 0.0361 AC: 551 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3468

East Asian (EAS) AF: 0.228 AC: 1180 AN: 5184

South Asian (SAS) AF: 0.122 AC: 588 AN: 4812

European-Finnish (FIN) AF: 0.121 AC: 1274 AN: 10560

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0524 AC: 3565 AN: 67984

Other (OTH) AF: 0.0568 AC: 120 AN: 2112

Alfa AF: 0.0557 Hom.: 617

Bravo AF: 0.0436

TwinsUK AF: 0.0475 AC: 176

ALSPAC AF: 0.0462 AC: 178

ESP6500AA AF: 0.0134 AC: 59

ESP6500EA AF: 0.0533 AC: 458

ExAC AF: 0.0734 AC: 8913

Asia WGS AF: 0.188 AC: 651 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EFCAB13-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.26	N
PhyloP100		1.1
Vest4		0.075
GERP RS		2.4
Mutation Taster		=174/26	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.56		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.56		Position offset: 30

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71377306; hg19: chr17-45425287; COSMIC: COSV58946778; COSMIC: COSV58946778;