rs13045180

Variant names:

• chr20-32943738-C-T
• rs13045180
• NM_001143967.2:c.2893C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001143967.2(EFCAB8):​c.2893C>T​(p.Gln965*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 416,780 control chromosomes in the GnomAD database, including 7,380 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.16 (2359 hom., cov: 32)
  • Exomes 𝑓: 0.18 (5021 hom.)
• Consequence: EFCAB8 NM_001143967.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 17 publications found

Genes affected

EFCAB8 (HGNC:34532): (EF-hand calcium binding domain 8) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143967.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB8	NM_001143967.2	MANE Select	c.2893C>T	p.Gln965*	stop_gained	Exon 23 of 27	NP_001137439.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB8	ENST00000400522.9	TSL:5 MANE Select	c.2893C>T	p.Gln965*	stop_gained	Exon 23 of 27	ENSP00000383366.5

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23758 AN: 152080 Hom.: 2358 Cov.: 32

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.184 AC: 48553 AN: 264582 Hom.: 5021 Cov.: 0 AF XY: 0.185 AC XY: 24679 AN XY: 133566

African (AFR) AF: 0.0492 AC: 357 AN: 7262

American (AMR) AF: 0.257 AC: 1911 AN: 7448

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 1832 AN: 9244

East Asian (EAS) AF: 0.0134 AC: 307 AN: 22902

South Asian (SAS) AF: 0.214 AC: 670 AN: 3128

European-Finnish (FIN) AF: 0.195 AC: 7135 AN: 36644

Middle Eastern (MID) AF: 0.224 AC: 657 AN: 2928

European-Non Finnish (NFE) AF: 0.207 AC: 32732 AN: 158366

Other (OTH) AF: 0.177 AC: 2952 AN: 16660

GnomAD4 genome AF: 0.156 AC: 23769 AN: 152198 Hom.: 2359 Cov.: 32 AF XY: 0.159 AC XY: 11815 AN XY: 74414

African (AFR) AF: 0.0480 AC: 1992 AN: 41532

American (AMR) AF: 0.241 AC: 3679 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3470

East Asian (EAS) AF: 0.0205 AC: 106 AN: 5178

South Asian (SAS) AF: 0.206 AC: 992 AN: 4822

European-Finnish (FIN) AF: 0.195 AC: 2062 AN: 10596

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13748 AN: 68000

Other (OTH) AF: 0.183 AC: 386 AN: 2112

Alfa AF: 0.187 Hom.: 12181

Bravo AF: 0.155

TwinsUK AF: 0.209 AC: 774

ALSPAC AF: 0.200 AC: 769

ESP6500AA AF: 0.0470 AC: 65

ESP6500EA AF: 0.217 AC: 692

Asia WGS AF: 0.122 AC: 427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	38
DANN	Benign	0.87
FATHMM_MKL	Benign	0.66	D
PhyloP100		1.4
Vest4		0.25
GERP RS		4.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs13045180; hg19: chr20-31531544; COSMIC: COSV107191065;