rs115808703

chr7-27182898-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005523.6(HOXA11):c.840C>T(p.Leu280=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000978 in 1,614,060 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00070 (7 hom.)
• Consequence: HOXA11 NM_005523.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 7-27182898-G-A is Benign according to our data. Variant chr7-27182898-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.44 with no splicing effect.
• BS2: High AC in GnomAd at 562 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXA11	NM_005523.6	c.840C>T	p.Leu280=	synonymous_variant	2/2	ENST00000006015.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXA11	ENST00000006015.4	c.840C>T	p.Leu280=	synonymous_variant	2/2	1	NM_005523.6	P1
HOXA11	ENST00000517402.1	c.750C>T	p.Leu250=	synonymous_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 562 AN: 152202 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00156 AC: 391 AN: 251366 Hom.: 4 AF XY: 0.00135 AC XY: 184 AN XY: 135894

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000370

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.000696 AC: 1017 AN: 1461740 Hom.: 7 Cov.: 31 AF XY: 0.000682 AC XY: 496 AN XY: 727178

Gnomad4 AFR exome AF: 0.0128

Gnomad4 AMR exome AF: 0.00286

Gnomad4 ASJ exome AF: 0.000880

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000285

Gnomad4 OTH exome AF: 0.00161

GnomAD4 genome AF: 0.00368 AC: 561 AN: 152320 Hom.: 2 Cov.: 33 AF XY: 0.00353 AC XY: 263 AN XY: 74484

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00190 Hom.: 1

Bravo AF: 0.00420

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000415

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 23, 2017

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	10
Dann	Benign	0.87

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: rs115808703; hg19: chr7-27222517;