rs3764962

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005257.6(GATA6):c.1620+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 1,597,168 control chromosomes in the GnomAD database, including 16,033 homozygotes. In-silico tool predicts 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 Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 8361 hom., cov: 32)

Exomes 𝑓: 0.033 ( 7672 hom. )

Consequence

GATA6
NM_005257.6 splice_region, intron

Scores

Splicing: ADA: 0.0004652

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.48

Variant links:

Genes affected

GATA6 (HGNC:4174): (GATA binding protein 6) This gene is a member of a small family of zinc finger transcription factors that play an important role in the regulation of cellular differentiation and organogenesis during vertebrate development. This gene is expressed during early embryogenesis and localizes to endo- and mesodermally derived cells during later embryogenesis and thereby plays an important role in gut, lung, and heart development. Mutations in this gene are associated with several congenital defects. [provided by RefSeq, Mar 2012]

GATA6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 18-22183050-A-G is Benign according to our data. Variant chr18-22183050-A-G is described in ClinVar as [Benign]. Clinvar id is 129133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-22183050-A-G is described in Lovd as [Benign]. Variant chr18-22183050-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA6	NM_005257.6 linkuse as main transcript	c.1620+7A>G		splice_region_variant, intron_variant		ENST00000269216.10
GATA6	XM_047437483.1 linkuse as main transcript	c.1620+7A>G		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA6	ENST00000269216.10 linkuse as main transcript	c.1620+7A>G		splice_region_variant, intron_variant		1	NM_005257.6	P1	Q92908-1
GATA6	ENST00000581694.1 linkuse as main transcript	c.1620+7A>G		splice_region_variant, intron_variant		1		P1	Q92908-1

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29177

AN:

152026

Hom.:

8319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.623

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.0508

Gnomad SAS

AF:

0.0303

Gnomad FIN

AF:

0.0205

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.147

GnomAD3 exomes

AF:

0.0690

AC:

17332

AN:

251094

Hom.:

3529

AF XY:

0.0556

AC XY:

7553

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.638

Gnomad AMR exome

AF:

0.0778

Gnomad ASJ exome

AF:

0.0163

Gnomad EAS exome

AF:

0.0537

Gnomad SAS exome

AF:

0.0312

Gnomad FIN exome

AF:

0.0175

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0496

GnomAD4 exome

AF:

0.0329

AC:

47574

AN:

1445024

Hom.:

7672

Cov.:

AF XY:

0.0307

AC XY:

22088

AN XY:

720064

show subpopulations

Gnomad4 AFR exome

AF:

0.642

Gnomad4 AMR exome

AF:

0.0809

Gnomad4 ASJ exome

AF:

0.0161

Gnomad4 EAS exome

AF:

0.0612

Gnomad4 SAS exome

AF:

0.0311

Gnomad4 FIN exome

AF:

0.0173

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.0614

GnomAD4 genome

AF:

0.192

AC:

29277

AN:

152144

Hom.:

8361

Cov.:

AF XY:

0.187

AC XY:

13939

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.624

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.0185

Gnomad4 EAS

AF:

0.0505

Gnomad4 SAS

AF:

0.0303

Gnomad4 FIN

AF:

0.0205

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.0930

Hom.:

1933

Bravo

AF:

0.219

Asia WGS

AF:

0.0870

AC:

303

AN:

3478

EpiCase

AF:

0.0142

EpiControl

AF:

0.0164

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 10, 2023	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Atrioventricular septal defect 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

Cadd

Benign

Dann

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00047

dbscSNV1_RF

Benign

0.068

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

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