17-62391965-C-T

Variant names:

• chr17-62391965-C-T
• rs61751980
• NM_173503.4:c.295C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_173503.4(EFCAB3):​c.295C>T​(p.Arg99*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00735 in 1,592,754 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0067 (11 hom., cov: 31)
  • Exomes 𝑓: 0.0074 (80 hom.)
• Consequence: EFCAB3 NM_173503.4 stop_gained, splice_region
• Scores: Splicing: ADA: 0.002096
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.656
• Publications: 10 publications found

Genes affected

EFCAB3 (HGNC:26379): (EF-hand calcium binding domain 3) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP6: Variant 17-62391965-C-T is Benign according to our data. Variant chr17-62391965-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 787599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173503.4. 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
	EFCAB3	NM_173503.4	MANE Select	c.295C>T	p.Arg99*	stop_gained splice_region	Exon 4 of 10	NP_775774.1	Q8N7B9-1
	EFCAB3	NM_001144933.2		c.451C>T	p.Arg151*	stop_gained splice_region	Exon 6 of 12	NP_001138405.1	Q8N7B9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB3	ENST00000305286.8	TSL:1 MANE Select	c.295C>T	p.Arg99*	stop_gained splice_region	Exon 4 of 10	ENSP00000302649.3	Q8N7B9-1
	EFCAB3	ENST00000450662.7	TSL:5	c.451C>T	p.Arg151*	stop_gained splice_region	Exon 6 of 12	ENSP00000403932.2	Q8N7B9-2
	EFCAB3	ENST00000520404.5	TSL:5	c.295C>T	p.Arg99*	stop_gained splice_region	Exon 4 of 7	ENSP00000429124.1	E5RJB7

Frequencies

GnomAD3 genomes AF: 0.00666 AC: 1012 AN: 151850 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.000895

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00315

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0451

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00624

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00774 AC: 1911 AN: 247058 AF XY: 0.00770

Gnomad AFR exome AF: 0.00149

Gnomad AMR exome AF: 0.00170

Gnomad ASJ exome AF: 0.00171

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0448

Gnomad NFE exome AF: 0.00702

Gnomad OTH exome AF: 0.00502

GnomAD4 exome AF: 0.00742 AC: 10697 AN: 1440792 Hom.: 80 Cov.: 30 AF XY: 0.00728 AC XY: 5216 AN XY: 716414

African (AFR) AF: 0.000903 AC: 30 AN: 33220

American (AMR) AF: 0.00188 AC: 82 AN: 43580

Ashkenazi Jewish (ASJ) AF: 0.00239 AC: 61 AN: 25560

East Asian (EAS) AF: 0.00 AC: 0 AN: 39434

South Asian (SAS) AF: 0.00116 AC: 95 AN: 81870

European-Finnish (FIN) AF: 0.0422 AC: 2221 AN: 52594

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5682

European-Non Finnish (NFE) AF: 0.00712 AC: 7828 AN: 1099458

Other (OTH) AF: 0.00638 AC: 379 AN: 59394

GnomAD4 genome AF: 0.00666 AC: 1012 AN: 151962 Hom.: 11 Cov.: 31 AF XY: 0.00819 AC XY: 608 AN XY: 74278

African (AFR) AF: 0.000892 AC: 37 AN: 41464

American (AMR) AF: 0.00315 AC: 48 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4806

European-Finnish (FIN) AF: 0.0451 AC: 475 AN: 10532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00624 AC: 424 AN: 67974

Other (OTH) AF: 0.00474 AC: 10 AN: 2108

Alfa AF: 0.00555 Hom.: 7

Bravo AF: 0.00389

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00500 AC: 43

ExAC AF: 0.00690 AC: 838

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	33
DANN	Benign	0.93
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.019	N
M_CAP	Benign	0.016	T
PhyloP100		-0.66
Vest4		0.27
GERP RS		-7.6
Mutation Taster		=181/19	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0021
dbscSNV1_RF	Benign	0.19
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: rs61751980; hg19: chr17-60469326; COSMIC: COSV100540135;