chr20-62476223-G-A

Variant names:

• chr20-62476223-G-A
• rs77067995
• NM_080473.5:c.-315C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080473.5(GATA5):​c.-315C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 152,248 control chromosomes in the GnomAD database, including 528 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 0.054 (528 hom., cov: 34)
• Consequence: GATA5 NM_080473.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 2 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: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA5	NM_080473.5	MANE Select	c.-315C>T		upstream_gene	N/A	NP_536721.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA5	ENST00000252997.3	TSL:1 MANE Select	c.-315C>T		upstream_gene	N/A	ENSP00000252997.2
	GATA5	ENST00000914293.1		c.-315C>T		upstream_gene	N/A	ENSP00000584352.1

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 8196 AN: 152130 Hom.: 524 Cov.: 34

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.0450

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00863

Gnomad OTH AF: 0.0416

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

GnomAD4 genome AF: 0.0540 AC: 8215 AN: 152248 Hom.: 528 Cov.: 34 AF XY: 0.0549 AC XY: 4091 AN XY: 74454

African (AFR) AF: 0.147 AC: 6112 AN: 41540

American (AMR) AF: 0.0225 AC: 344 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

East Asian (EAS) AF: 0.0449 AC: 232 AN: 5168

South Asian (SAS) AF: 0.160 AC: 775 AN: 4830

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00863 AC: 587 AN: 68004

Other (OTH) AF: 0.0426 AC: 90 AN: 2112

Alfa AF: 0.0346 Hom.: 45

Bravo AF: 0.0563

Asia WGS AF: 0.111 AC: 385 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.3
DANN	Benign	0.80
PhyloP100		-1.3
PromoterAI		-0.0050	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs77067995; hg19: chr20-61051279;