rs112588760

Variant names:

• chr17-29969104-G-C
• rs112588760
• NM_198529.4:c.504G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_198529.4(EFCAB5):​c.504G>C​(p.Leu168Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0054 in 1,613,764 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (30 hom.)
• Consequence: EFCAB5 NM_198529.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.377
• Publications: 4 publications found

Genes affected

EFCAB5 (HGNC:24801): (EF-hand calcium binding domain 5) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 17-29969104-G-C is Benign according to our data. Variant chr17-29969104-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2647618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.377 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198529.4. 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
	EFCAB5	NM_198529.4	MANE Select	c.504G>C	p.Leu168Leu	synonymous	Exon 4 of 23	NP_940931.3	A4FU69-1
	EFCAB5	NM_001145053.2		c.336G>C	p.Leu112Leu	synonymous	Exon 4 of 15	NP_001138525.2	A4FU69-5
	EFCAB5	NR_026738.2		n.667G>C		non_coding_transcript_exon	Exon 4 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB5	ENST00000394835.8	TSL:1 MANE Select	c.504G>C	p.Leu168Leu	synonymous	Exon 4 of 23	ENSP00000378312.3	A4FU69-1
	EFCAB5	ENST00000440741.7	TSL:1	n.504G>C		non_coding_transcript_exon	Exon 4 of 16	ENSP00000393095.2	A4FU69-2
	EFCAB5	ENST00000536908.6	TSL:2	c.336G>C	p.Leu112Leu	synonymous	Exon 4 of 15	ENSP00000440619.2	A4FU69-5

Frequencies

GnomAD3 genomes AF: 0.00473 AC: 720 AN: 152160 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00760

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00433 AC: 1077 AN: 248540 AF XY: 0.00467

Gnomad AFR exome AF: 0.00104

Gnomad AMR exome AF: 0.00244

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00704

Gnomad OTH exome AF: 0.00513

GnomAD4 exome AF: 0.00547 AC: 7991 AN: 1461486 Hom.: 30 Cov.: 31 AF XY: 0.00538 AC XY: 3914 AN XY: 726990

African (AFR) AF: 0.00111 AC: 37 AN: 33478

American (AMR) AF: 0.00302 AC: 135 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 309 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.000835 AC: 72 AN: 86214

European-Finnish (FIN) AF: 0.00114 AC: 61 AN: 53382

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5766

European-Non Finnish (NFE) AF: 0.00636 AC: 7066 AN: 1111776

Other (OTH) AF: 0.00482 AC: 291 AN: 60372

GnomAD4 genome AF: 0.00473 AC: 721 AN: 152278 Hom.: 3 Cov.: 32 AF XY: 0.00422 AC XY: 314 AN XY: 74460

African (AFR) AF: 0.00159 AC: 66 AN: 41568

American (AMR) AF: 0.00405 AC: 62 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 47 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00762 AC: 518 AN: 68014

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00720 Hom.: 5

Bravo AF: 0.00464

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00747

EpiControl AF: 0.00784

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.2
DANN	Benign	0.69
PhyloP100		0.38
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism

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: rs112588760; hg19: chr17-28296122; COSMIC: COSV57930633; COSMIC: COSV57930633;