dbSNP rs1941083: GATA6:c.*77A>G (chr18-22200900-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_005257.6(GATA6):c.*77A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,449,538 control chromosomes in the GnomAD database, including 14,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1470 hom., cov: 33)

Exomes 𝑓: 0.14 ( 13476 hom. )

Consequence

GATA6
NM_005257.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.116

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:

ENSG00000266283 (HGNC:):

ENSG00000266283 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 18-22200900-A-G is Benign according to our data. Variant chr18-22200900-A-G is described in ClinVar as [Benign]. Clinvar id is 1227720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA6	NM_005257.6 link	c.*77A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000269216.10	NP_005248.2	Q92908-1
GATA6	XM_047437483.1 link	c.*77A>G		3_prime_UTR_variant	Exon 7 of 7		XP_047293439.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GATA6	ENST00000269216.10 link	c.*77A>G	3_prime_UTR_variant	Exon 7 of 7	1	NM_005257.6	ENSP00000269216.3	Q92908-1
ENSG00000266283	ENST00000583442.1 link	n.489T>C	non_coding_transcript_exon_variant	Exon 2 of 2	3
GATA6	ENST00000581694.1 link	c.*77A>G	downstream_gene_variant		1		ENSP00000462313.1	Q92908-1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18651

AN:

152152

Hom.:

1464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.0978

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.126

GnomAD4 exome

AF:

0.142

AC:

183992

AN:

1297268

Hom.:

13476

Cov.:

AF XY:

0.143

AC XY:

91494

AN XY:

641252

show subpopulations

Gnomad4 AFR exome

AF:

0.0246

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.152

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.123

AC:

18667

AN:

152270

Hom.:

1470

Cov.:

AF XY:

0.128

AC XY:

9546

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0316

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.0978

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.142

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.145

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.133

Hom.:

187

Bravo

AF:

0.121

Asia WGS

AF:

0.165

AC:

576

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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