chr17-29968791-A-G

Variant names:

• chr17-29968791-A-G
• rs185083507
• NM_198529.4:c.191A>G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_198529.4(EFCAB5):​c.191A>G​(p.Glu64Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00041 in 1,480,542 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: EFCAB5 NM_198529.4 missense, splice_region
• Scores: Splicing: ADA: 0.3912
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.05

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052396953).
• BP6: Variant 17-29968791-A-G is Benign according to our data. Variant chr17-29968791-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3040137.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB5	NM_198529.4	c.191A>G	p.Glu64Gly	missense_variant, splice_region_variant	Exon 4 of 23	ENST00000394835.8	NP_940931.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB5	ENST00000394835.8	c.191A>G	p.Glu64Gly	missense_variant, splice_region_variant	Exon 4 of 23	1	NM_198529.4	ENSP00000378312.3

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 281 AN: 152156 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00632

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000513 AC: 60 AN: 117006 Hom.: 0 AF XY: 0.000320 AC XY: 20 AN XY: 62438

Gnomad AFR exome AF: 0.00659

Gnomad AMR exome AF: 0.000341

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000133

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000597

Gnomad OTH exome AF: 0.000641

GnomAD4 exome AF: 0.000242 AC: 321 AN: 1328268 Hom.: 1 Cov.: 30 AF XY: 0.000240 AC XY: 156 AN XY: 649394

Gnomad4 AFR exome AF: 0.00701

Gnomad4 AMR exome AF: 0.000480

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000630

Gnomad4 OTH exome AF: 0.000568

GnomAD4 genome AF: 0.00188 AC: 286 AN: 152274 Hom.: 1 Cov.: 31 AF XY: 0.00191 AC XY: 142 AN XY: 74464

Gnomad4 AFR AF: 0.00645

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000460 Hom.: 2

Bravo AF: 0.00229

ESP6500AA AF: 0.00550 AC: 19

ESP6500EA AF: 0.000127 AC: 1

ExAC AF: 0.000396 AC: 43

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EFCAB5-related disorder Benign:1

Jun 18, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0049	.;.;T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.55	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.0052	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	.;.;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.9	D;N;N;.
REVEL	Benign	0.070
Sift	Uncertain	0.0090	D;D;D;.
Sift4G	Uncertain	0.026	D;D;T;.
Polyphen		0.98	.;.;D;.
Vest4		0.20, 0.17
MVP		0.46
MPC		0.11
ClinPred		0.030	T
GERP RS		5.1
Varity_R		0.15
gMVP		0.076

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.39
dbscSNV1_RF	Benign	0.63
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

Publications

LitVar

Other links and lift over

dbSNP: rs185083507; hg19: chr17-28295809;