Variant chr7-27182790-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005523.6(HOXA11):c.*6C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0095 in 1,553,688 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0097 ( 81 hom. )

Consequence

HOXA11
NM_005523.6 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.715

Variant links:

Genes affected

HOXA11 (HGNC:5101): (homeobox A11) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. This gene is involved in the regulation of uterine development and is required for female fertility. Mutations in this gene can cause radio-ulnar synostosis with amegakaryocytic thrombocytopenia. [provided by RefSeq, Jul 2008]

HOXA11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 7-27182790-G-A is Benign according to our data. Variant chr7-27182790-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1336029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00973 (13634/1401348) while in subpopulation MID AF= 0.0281 (159/5660). AF 95% confidence interval is 0.0245. There are 81 homozygotes in gnomad4_exome. There are 6737 alleles in male gnomad4_exome subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA11	NM_005523.6 linkuse as main transcript	c.*6C>T		3_prime_UTR_variant	2/2	ENST00000006015.4	NP_005514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA11	ENST00000006015.4 linkuse as main transcript	c.*6C>T		3_prime_UTR_variant	2/2	1	NM_005523.6	ENSP00000006015	P1
HOXA11	ENST00000517402.1 linkuse as main transcript	c.*6C>T		3_prime_UTR_variant	3/3	1		ENSP00000448962

Frequencies

GnomAD3 genomes

AF:

0.00739

AC:

1125

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00877

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00396

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00853

AC:

2138

AN:

250656

Hom.:

AF XY:

0.00838

AC XY:

1137

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.00200

Gnomad AMR exome

AF:

0.00873

Gnomad ASJ exome

AF:

0.0192

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.00494

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.00973

AC:

13634

AN:

1401348

Hom.:

Cov.:

AF XY:

0.00961

AC XY:

6737

AN XY:

700902

show subpopulations

Gnomad4 AFR exome

AF:

0.00181

Gnomad4 AMR exome

AF:

0.00947

Gnomad4 ASJ exome

AF:

0.0187

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00277

Gnomad4 FIN exome

AF:

0.00477

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.00738

AC:

1125

AN:

152340

Hom.:

Cov.:

AF XY:

0.00664

AC XY:

495

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00204

Gnomad4 AMR

AF:

0.00876

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00396

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.00832

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0158

EpiControl

AF:

0.0135

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	HOXA11: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 17, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.79

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