rs112195861

Variant names:

• chr20-62464564-G-T
• rs112195861
• NM_080473.5:c.*272C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_080473.5(GATA5):​c.*272C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 342,646 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: GATA5 NM_080473.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.624
• Publications: 0 publications found

Genes affected

GATA5 (HGNC:15802): (GATA binding protein 5) The protein encoded by this gene is a transcription factor that contains two GATA-type zinc fingers. The encoded protein is known to bind to hepatocyte nuclear factor-1alpha (HNF-1alpha), and this interaction is essential for cooperative activation of the intestinal lactase-phlorizin hydrolase promoter. In other organisms, similar proteins may be involved in the establishment of cardiac smooth muscle cell diversity. [provided by RefSeq, Jul 2008]

GATA5 Gene-Disease associations (from GenCC):

• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial bicuspid aortic valve

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tetralogy of fallot

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart defects, multiple types, 5

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-62464564-G-T is Benign according to our data. Variant chr20-62464564-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1208316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00573 (873/152364) while in subpopulation AFR AF = 0.019 (790/41580). AF 95% confidence interval is 0.0179. There are 6 homozygotes in GnomAd4. There are 425 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 873 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080473.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA5	NM_080473.5	MANE Select	c.*272C>A		3_prime_UTR	Exon 7 of 7	NP_536721.1	Q9BWX5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA5	ENST00000252997.3	TSL:1 MANE Select	c.*272C>A		3_prime_UTR	Exon 7 of 7	ENSP00000252997.2	Q9BWX5
	GATA5	ENST00000914293.1		c.*272C>A		3_prime_UTR	Exon 7 of 7	ENSP00000584352.1
	GATA5	ENST00000861188.1		c.*272C>A		3_prime_UTR	Exon 7 of 7	ENSP00000531247.1

Frequencies

GnomAD3 genomes AF: 0.00574 AC: 874 AN: 152246 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000658

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.00113 AC: 215 AN: 190282 Hom.: 0 Cov.: 0 AF XY: 0.00108 AC XY: 103 AN XY: 95618

African (AFR) AF: 0.0210 AC: 115 AN: 5482

American (AMR) AF: 0.00171 AC: 9 AN: 5268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7464

East Asian (EAS) AF: 0.00 AC: 0 AN: 16242

South Asian (SAS) AF: 0.000213 AC: 1 AN: 4690

European-Finnish (FIN) AF: 0.000470 AC: 7 AN: 14902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1030

European-Non Finnish (NFE) AF: 0.000532 AC: 65 AN: 122246

Other (OTH) AF: 0.00139 AC: 18 AN: 12958

GnomAD4 genome AF: 0.00573 AC: 873 AN: 152364 Hom.: 6 Cov.: 33 AF XY: 0.00570 AC XY: 425 AN XY: 74516

African (AFR) AF: 0.0190 AC: 790 AN: 41580

American (AMR) AF: 0.00261 AC: 40 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.000658 AC: 7 AN: 10632

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68032

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00291 Hom.: 0

Bravo AF: 0.00656

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.88
DANN	Benign	0.52
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs112195861; hg19: chr20-61039620;