dbSNP rs201197242: EFCAB5:c.42+1G>A (chr17-29941839-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

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:1O:1

Conservation

PhyloP100: 4.02

Variant links:

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]

EFCAB5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 link	c.42+1G>A		splice_donor_variant, intron_variant	Intron 1 of 22	ENST00000394835.8	NP_940931.3	A4FU69-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB5	ENST00000394835.8 link	c.42+1G>A		splice_donor_variant, intron_variant	Intron 1 of 22	1	NM_198529.4	ENSP00000378312.3		A4FU69-1

Frequencies

GnomAD3 genomes

AF:

0.00529

AC:

804

AN:

152126

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00527

AC:

1216

AN:

230648

Hom.:

AF XY:

0.00527

AC XY:

655

AN XY:

124406

show subpopulations

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 SAS 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.:

Cov.:

AF XY:

0.00398

AC XY:

2866

AN XY:

720196

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000874

Gnomad4 ASJ exome

AF:

0.00707

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.0176

Gnomad4 NFE exome

AF:

0.00372

Gnomad4 OTH exome

AF:

0.00364

GnomAD4 genome

AF:

0.00528

AC:

804

AN:

152242

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

426

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0177

Gnomad4 NFE

AF:

0.00834

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00645

Hom.:

Bravo

AF:

0.00302

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000267

AC:

ESP6500EA

AF:

0.00608

AC:

ExAC

AF:

0.00481

AC:

580

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

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. -

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EFCAB5: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Benign

0.96

Eigen

Pathogenic

0.88

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.85

GERP RS

4.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over