chr18-22170849-C-T

Position:

• chr18-22170849-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005257.6(GATA6):​c.-37-259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 502,912 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0098 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (8 hom.)
• Consequence: GATA6 NM_005257.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.334

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 18-22170849-C-T is Benign according to our data. Variant chr18-22170849-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1186949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00979 (1490/152142) while in subpopulation AFR AF= 0.0279 (1156/41488). AF 95% confidence interval is 0.0265. There are 9 homozygotes in gnomad4. There are 703 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1490 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA6	NM_005257.6	c.-37-259C>T		intron_variant		ENST00000269216.10	NP_005248.2
GATA6	XM_047437483.1	c.-37-259C>T		intron_variant			XP_047293439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA6	ENST00000269216.10	c.-37-259C>T		intron_variant		1	NM_005257.6	ENSP00000269216	P1

Frequencies

GnomAD3 genomes AF: 0.00983 AC: 1494 AN: 152024 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00354 AC: 1241 AN: 350770 Hom.: 8 AF XY: 0.00333 AC XY: 609 AN XY: 182784

Gnomad4 AFR exome AF: 0.0296

Gnomad4 AMR exome AF: 0.00372

Gnomad4 ASJ exome AF: 0.00665

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00163

Gnomad4 FIN exome AF: 0.000700

Gnomad4 NFE exome AF: 0.00299

Gnomad4 OTH exome AF: 0.00508

GnomAD4 genome AF: 0.00979 AC: 1490 AN: 152142 Hom.: 9 Cov.: 32 AF XY: 0.00945 AC XY: 703 AN XY: 74386

Gnomad4 AFR AF: 0.0279

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00779

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00278

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00195 Hom.: 1

Bravo AF: 0.0112

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.9
DANN	Benign	0.82

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: rs115825500; hg19: chr18-19750810;