NM_001142556.2:c.2125+150G>A

Variant names:

• chr5-163490702-G-A
• rs10515860
• NM_001142556.2:c.2125+150G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HMMR	NM_001142556.2	c.2125+150G>A		intron_variant	Intron 17 of 17	ENST00000393915.9	NP_001136028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMMR	ENST00000393915.9	c.2125+150G>A		intron_variant	Intron 17 of 17	1	NM_001142556.2	ENSP00000377492.4

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

African (AFR) AF: 0.0253 AC: 299 AN: 11802

American (AMR) AF: 0.0865 AC: 1361 AN: 15728

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 1522 AN: 15044

East Asian (EAS) AF: 0.0343 AC: 1023 AN: 29834

South Asian (SAS) AF: 0.146 AC: 6761 AN: 46354

European-Finnish (FIN) AF: 0.143 AC: 6022 AN: 42144

Middle Eastern (MID) AF: 0.100 AC: 212 AN: 2114

European-Non Finnish (NFE) AF: 0.118 AC: 34798 AN: 294810

Other (OTH) AF: 0.108 AC: 2882 AN: 26772

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

African (AFR) AF: 0.0237 AC: 984 AN: 41550

American (AMR) AF: 0.0988 AC: 1512 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3472

East Asian (EAS) AF: 0.0508 AC: 263 AN: 5176

South Asian (SAS) AF: 0.145 AC: 701 AN: 4828

European-Finnish (FIN) AF: 0.160 AC: 1695 AN: 10588

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8312 AN: 68014

Other (OTH) AF: 0.0922 AC: 195 AN: 2116

Alfa AF: 0.107 Hom.: 1152

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
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10515860; hg19: chr5-162917708;