rs6968828

Positions:

• chr7-27183944-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005523.6(HOXA11):​c.709+492C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,964 control chromosomes in the GnomAD database, including 22,133 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 0.54 (22133 hom., cov: 32)
• Consequence: HOXA11 NM_005523.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44

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=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA11	NM_005523.6	c.709+492C>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+492C>A		intron_variant		1	NM_005523.6	ENSP00000006015	P1
HOXA11	ENST00000517402.1	c.618+492C>A		intron_variant		1		ENSP00000448962

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81562 AN: 151846 Hom.: 22127 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.537 AC: 81592 AN: 151964 Hom.: 22133 Cov.: 32 AF XY: 0.537 AC XY: 39879 AN XY: 74252

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.568

Alfa AF: 0.565 Hom.: 45254

Bravo AF: 0.538

Asia WGS AF: 0.574 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.93

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: rs6968828; hg19: chr7-27223563;