18-22177952-G-T

Position:

• chr18-22177952-G-T

Variant summary

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

The NM_005257.6(GATA6):​c.1302+831G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.19 (2424 hom., cov: 16)
• Consequence: GATA6 NM_005257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA6	NM_005257.6	c.1302+831G>T		intron_variant		ENST00000269216.10	NP_005248.2
GATA6	XM_047437483.1	c.1302+831G>T		intron_variant			XP_047293439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA6	ENST00000269216.10	c.1302+831G>T		intron_variant		1	NM_005257.6	ENSP00000269216.3
GATA6	ENST00000581694.1	c.1302+831G>T		intron_variant		1		ENSP00000462313.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 14664 AN: 77886 Hom.: 2409 Cov.: 16

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.0189

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.189 AC: 14705 AN: 77924 Hom.: 2424 Cov.: 16 AF XY: 0.194 AC XY: 7211 AN XY: 37148

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.0697

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0485

Gnomad4 NFE AF: 0.0463

Gnomad4 OTH AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.34

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: rs7235350; hg19: chr18-19757913;