rs9957475

Positions:

• chr18-22180950-T-C
• chr18-22180950-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005257.6(GATA6):​c.1303-503T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 151,004 control chromosomes in the GnomAD database, including 5,052 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (5052 hom., cov: 32)
• Consequence: GATA6 NM_005257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA6	NM_005257.6	c.1303-503T>C		intron_variant		ENST00000269216.10	NP_005248.2
GATA6	XM_047437483.1	c.1303-503T>C		intron_variant			XP_047293439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA6	ENST00000269216.10	c.1303-503T>C		intron_variant		1	NM_005257.6	ENSP00000269216.3
GATA6	ENST00000581694.1	c.1303-503T>C		intron_variant		1		ENSP00000462313.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23300 AN: 150884 Hom.: 5033 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.0191

Gnomad EAS AF: 0.0914

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.0269

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.118

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.155 AC: 23374 AN: 151004 Hom.: 5052 Cov.: 32 AF XY: 0.152 AC XY: 11182 AN XY: 73722

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.0848

Gnomad4 ASJ AF: 0.0191

Gnomad4 EAS AF: 0.0912

Gnomad4 SAS AF: 0.0365

Gnomad4 FIN AF: 0.0269

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0962 Hom.: 377

Bravo AF: 0.174

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.27

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: rs9957475; hg19: chr18-19760911;