rs61751980

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-62391965-C-A
• chr17-62391965-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_173503.4(EFCAB3):​c.295C>A​(p.Arg99Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,440,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: EFCAB3 NM_173503.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0005473
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.656 with no splicing effect.

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>A	p.Arg99Arg	splice_region synonymous	Exon 4 of 10	NP_775774.1	Q8N7B9-1
	EFCAB3	NM_001144933.2		c.451C>A	p.Arg151Arg	splice_region synonymous	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>A	p.Arg99Arg	splice_region synonymous	Exon 4 of 10	ENSP00000302649.3	Q8N7B9-1
	EFCAB3	ENST00000450662.7	TSL:5	c.451C>A	p.Arg151Arg	splice_region synonymous	Exon 6 of 12	ENSP00000403932.2	Q8N7B9-2
	EFCAB3	ENST00000520404.5	TSL:5	c.295C>A	p.Arg99Arg	splice_region synonymous	Exon 4 of 7	ENSP00000429124.1	E5RJB7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000486 AC: 7 AN: 1440818 Hom.: 0 Cov.: 30 AF XY: 0.00000558 AC XY: 4 AN XY: 716426

African (AFR) AF: 0.00 AC: 0 AN: 33220

American (AMR) AF: 0.00 AC: 0 AN: 43580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25560

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 81870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00000637 AC: 7 AN: 1099478

Other (OTH) AF: 0.00 AC: 0 AN: 59394

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.45
PhyloP100		-0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00055
dbscSNV1_RF	Benign	0.39
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;