rs9944560

chr18-22184305-T-C

Variant summary

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

The NM_005257.6(GATA6):c.1620+1262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 151,554 control chromosomes in the GnomAD database, including 6,588 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 0.17 (6588 hom., cov: 32)
• Consequence: GATA6 NM_005257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA6	NM_005257.6	c.1620+1262T>C		intron_variant		ENST00000269216.10
GATA6	XM_047437483.1	c.1620+1262T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA6	ENST00000269216.10	c.1620+1262T>C		intron_variant		1	NM_005257.6	P1
GATA6	ENST00000581694.1	c.1620+1262T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26315 AN: 151438 Hom.: 6557 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.174 AC: 26403 AN: 151554 Hom.: 6588 Cov.: 32 AF XY: 0.171 AC XY: 12650 AN XY: 74096

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.0940

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.0861

Gnomad4 SAS AF: 0.0357

Gnomad4 FIN AF: 0.0258

Gnomad4 NFE AF: 0.0128

Gnomad4 OTH AF: 0.131

Alfa AF: 0.136 Hom.: 488

Bravo AF: 0.196

Asia WGS AF: 0.102 AC: 355 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.93
Dann	Benign	0.45

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: rs9944560; hg19: chr18-19764266;