7-27184152-C-T

Position:

• chr7-27184152-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_005523.6(HOXA11):​c.709+284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,934 control chromosomes in the GnomAD database, including 4,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (4531 hom., cov: 32)
• Consequence: HOXA11 NM_005523.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.642

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 7-27184152-C-T is Benign according to our data. Variant chr7-27184152-C-T is described in ClinVar as [Benign]. Clinvar id is 1271624.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA11	NM_005523.6	c.709+284G>A		intron_variant		ENST00000006015.4	NP_005514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA11	ENST00000006015.4	c.709+284G>A		intron_variant		1	NM_005523.6	ENSP00000006015	P1
HOXA11	ENST00000517402.1	c.618+284G>A		intron_variant		1		ENSP00000448962

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36333 AN: 151816 Hom.: 4531 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.239 AC: 36340 AN: 151934 Hom.: 4531 Cov.: 32 AF XY: 0.237 AC XY: 17582 AN XY: 74264

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.0342

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.222

Alfa AF: 0.217 Hom.: 1396

Bravo AF: 0.230

Asia WGS AF: 0.158 AC: 549 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.92

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: rs7801581; hg19: chr7-27223771;