Genetic Variant NM_080473.5:c.*272C>A (chr20-62464564-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.624

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 873 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA5	NM_080473.5 link	c.*272C>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000252997.3	NP_536721.1	Q9BWX5
GATA5	XM_006723699.3 link	c.*272C>A		3_prime_UTR_variant	Exon 7 of 7		XP_006723762.1	Q9BWX5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA5	ENST00000252997 link	c.*272C>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_080473.5	ENSP00000252997.2		Q9BWX5

Frequencies

GnomAD3 genomes

AF:

0.00574

AC:

874

AN:

152246

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00108

AC XY:

103

AN XY:

95618

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.00171

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000213

Gnomad4 FIN exome

AF:

0.000470

Gnomad4 NFE exome

AF:

0.000532

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00573

AC:

873

AN:

152364

Hom.:

Cov.:

AF XY:

0.00570

AC XY:

425

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0190

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000658

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00291

Hom.:

Bravo

AF:

0.00656

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 31, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.88

DANN

Benign

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over