rs3756648

Positions:

• chr5-163464888-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.225+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 809,290 control chromosomes in the GnomAD database, including 78,685 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 0.41 (13424 hom., cov: 33)
  • Exomes 𝑓: 0.44 (65261 hom.)
• Consequence: HMMR NM_001142556.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMMR	NM_001142556.2	c.225+86G>A		intron_variant		ENST00000393915.9	NP_001136028.1
HMMR	NM_012484.3	c.225+86G>A		intron_variant			NP_036616.2
HMMR	NM_012485.3	c.225+86G>A		intron_variant			NP_036617.2
HMMR	NM_001142557.2	c.12+4150G>A		intron_variant			NP_001136029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMMR	ENST00000393915.9	c.225+86G>A		intron_variant		1	NM_001142556.2	ENSP00000377492.4
HMMR	ENST00000520345.5	c.-73+86G>A		intron_variant		2		ENSP00000428481.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62557 AN: 151950 Hom.: 13421 Cov.: 33

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.435 AC: 286199 AN: 657222 Hom.: 65261 Cov.: 9 AF XY: 0.429 AC XY: 150986 AN XY: 351812

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.439

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.490

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.411 AC: 62571 AN: 152068 Hom.: 13424 Cov.: 33 AF XY: 0.406 AC XY: 30187 AN XY: 74360

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.429

Alfa AF: 0.448 Hom.: 3086

Bravo AF: 0.411

Asia WGS AF: 0.267 AC: 930 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.47

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: rs3756648; hg19: chr5-162891894;