rs10515860

chr5-163490702-G-A

Variant summary

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

The NM_001142556.2(HMMR):c.2125+150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 636,852 control chromosomes in the GnomAD database, including 4,413 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 0.093 (814 hom., cov: 33)
  • Exomes 𝑓: 0.11 (3599 hom.)
• Consequence: HMMR NM_001142556.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

Genes affected

HMMR (HGNC:5012): (hyaluronan mediated motility receptor) The protein encoded by this gene is involved in cell motility. It is expressed in breast tissue and together with other proteins, it forms a complex with BRCA1 and BRCA2, thus is potentially associated with higher risk of breast cancer. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Dec 2008]

HMMR-AS1 (HGNC:49149): (HMMR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMMR	NM_001142556.2	c.2125+150G>A		intron_variant		ENST00000393915.9
HMMR-AS1	NR_109892.1	n.468-1319C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMMR	ENST00000393915.9	c.2125+150G>A		intron_variant		1	NM_001142556.2	A2
HMMR-AS1	ENST00000521666.1	n.592+2741C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 14103 AN: 152132 Hom.: 811 Cov.: 33

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0509

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0864

GnomAD4 exome AF: 0.113 AC: 54880 AN: 484602 Hom.: 3599 AF XY: 0.115 AC XY: 29807 AN XY: 259640

Gnomad4 AFR exome AF: 0.0253

Gnomad4 AMR exome AF: 0.0865

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.0343

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.0927 AC: 14113 AN: 152250 Hom.: 814 Cov.: 33 AF XY: 0.0955 AC XY: 7108 AN XY: 74448

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.0988

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.0508

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0922

Alfa AF: 0.110 Hom.: 901

Bravo AF: 0.0822

Asia WGS AF: 0.0930 AC: 323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.1
Dann	Benign	0.34

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: rs10515860; hg19: chr5-162917708;