rs78865644

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-47361422-C-T
• chr17-47361422-C-A

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 17 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 -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 VariationId is 3041441.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 6 gene

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.706C>T	p.Arg236*	stop_gained	Exon 10 of 25	NP_689560.3
	EFCAB13	NM_001426585.1		c.706C>T	p.Arg236*	stop_gained	Exon 9 of 23	NP_001413514.1
	EFCAB13	NM_001426586.1		c.562C>T	p.Arg188*	stop_gained	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.706C>T	p.Arg236*	stop_gained	Exon 10 of 25	ENSP00000332111.2	Q8IY85-1
	EFCAB13	ENST00000517484.5	TSL:2	c.518-9015C>T		intron	N/A	ENSP00000430048.1	Q8IY85-2
	EFCAB13	ENST00000517310.5	TSL:2	c.74-9015C>T		intron	N/A	ENSP00000466136.1	K7ELL9

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

GnomAD2 exomes AF: 0.00791 AC: 1987 AN: 251326 AF XY: 0.00837

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 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

African (AFR) AF: 0.00179 AC: 60 AN: 33460

American (AMR) AF: 0.00834 AC: 373 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 354 AN: 26118

East Asian (EAS) AF: 0.000278 AC: 11 AN: 39616

South Asian (SAS) AF: 0.00122 AC: 105 AN: 86218

European-Finnish (FIN) AF: 0.00588 AC: 314 AN: 53402

Middle Eastern (MID) AF: 0.0125 AC: 72 AN: 5762

European-Non Finnish (NFE) AF: 0.0111 AC: 12356 AN: 1111742

Other (OTH) AF: 0.00883 AC: 533 AN: 60362

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

African (AFR) AF: 0.00190 AC: 79 AN: 41476

American (AMR) AF: 0.0124 AC: 190 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3466

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.00625 AC: 66 AN: 10566

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0106 AC: 719 AN: 67988

Other (OTH) AF: 0.0204 AC: 43 AN: 2110

Alfa AF: 0.00988 Hom.: 38

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

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	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
PhyloP100		1.5
Vest4		0.15
GERP RS		1.7
Mutation Taster		=148/52	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs78865644; hg19: chr17-45438788; COSMIC: COSV58949015;