17-29941839-G-A

Variant names:

• chr17-29941839-G-A
• rs201197242
• NM_198529.4:c.42+1G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_198529.4(EFCAB5):​c.42+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.00393 in 1,602,532 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (64 hom.)
• Consequence: EFCAB5 NM_198529.4 splice_donor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 4.02

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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 17-29941839-G-A is Benign according to our data. Variant chr17-29941839-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 585108.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB5	NM_198529.4	c.42+1G>A		splice_donor_variant, intron_variant	Intron 1 of 22	ENST00000394835.8	NP_940931.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB5	ENST00000394835.8	c.42+1G>A		splice_donor_variant, intron_variant	Intron 1 of 22	1	NM_198529.4	ENSP00000378312.3

Frequencies

GnomAD3 genomes AF: 0.00529 AC: 804 AN: 152126 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00833

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00527 AC: 1216 AN: 230648 AF XY: 0.00527

Gnomad AFR exome AF: 0.0000716

Gnomad AMR exome AF: 0.000853

Gnomad ASJ exome AF: 0.00567

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0197

Gnomad NFE exome AF: 0.00679

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00378 AC: 5486 AN: 1450290 Hom.: 64 Cov.: 31 AF XY: 0.00398 AC XY: 2866 AN XY: 720196

Gnomad4 AFR exome AF: 0.000210 AC: 7 AN: 33276

Gnomad4 AMR exome AF: 0.000874 AC: 38 AN: 43458

Gnomad4 ASJ exome AF: 0.00707 AC: 182 AN: 25756

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39480

Gnomad4 SAS exome AF: 0.0000119 AC: 1 AN: 84152

Gnomad4 FIN exome AF: 0.0176 AC: 929 AN: 52810

Gnomad4 NFE exome AF: 0.00372 AC: 4110 AN: 1105648

Gnomad4 Remaining exome AF: 0.00364 AC: 218 AN: 59952

GnomAD4 genome AF: 0.00528 AC: 804 AN: 152242 Hom.: 10 Cov.: 32 AF XY: 0.00572 AC XY: 426 AN XY: 74448

Gnomad4 AFR AF: 0.000313 AC: 0.000312997 AN: 0.000312997

Gnomad4 AMR AF: 0.000392 AC: 0.000392362 AN: 0.000392362

Gnomad4 ASJ AF: 0.00663 AC: 0.00662824 AN: 0.00662824

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.0177 AC: 0.0177425 AN: 0.0177425

Gnomad4 NFE AF: 0.00834 AC: 0.00833578 AN: 0.00833578

Gnomad4 OTH AF: 0.00331 AC: 0.00331439 AN: 0.00331439

Alfa AF: 0.00629 Hom.: 24

Bravo AF: 0.00302

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000267 AC: 1

ESP6500EA AF: 0.00608 AC: 50

ExAC AF: 0.00481 AC: 580

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1 Other:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EFCAB5: BS2 -

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Benign	0.96
Eigen	Pathogenic	0.88
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.85	D
GERP RS		4.1
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.95
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.31		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201197242; hg19: chr17-28268857; COSMIC: COSV57932407; COSMIC: COSV57932407;