rs61731977

chr18-22181500-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005257.6(GATA6):c.1350A>G(p.Thr450=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00087 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: GATA6 NM_005257.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.309

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 18-22181500-A-G is Benign according to our data. Variant chr18-22181500-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 472911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-22181500-A-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.309 with no splicing effect.
• BS2: High AC in GnomAd at 128 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA6	NM_005257.6	c.1350A>G	p.Thr450=	synonymous_variant	4/7	ENST00000269216.10
GATA6	XM_047437483.1	c.1350A>G	p.Thr450=	synonymous_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA6	ENST00000269216.10	c.1350A>G	p.Thr450=	synonymous_variant	4/7	1	NM_005257.6	P1
GATA6	ENST00000581694.1	c.1350A>G	p.Thr450=	synonymous_variant	3/6	1		P1

Frequencies

GnomAD3 genomes AF: 0.000841 AC: 128 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000175 AC: 44 AN: 251494 Hom.: 0 AF XY: 0.000125 AC XY: 17 AN XY: 135922

Gnomad AFR exome AF: 0.00258

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000581 AC: 85 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29 AN XY: 727234

Gnomad4 AFR exome AF: 0.00182

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000248

GnomAD4 genome AF: 0.000867 AC: 132 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.000739 AC XY: 55 AN XY: 74474

Gnomad4 AFR AF: 0.00306

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000558 Hom.: 0

Bravo AF: 0.00112

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 10, 2020

- -

Atrioventricular septal defect 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	5.6
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs61731977; hg19: chr18-19761461;