5-163469850-T-C

Position:

• chr5-163469850-T-C

Variant summary

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

The NM_001142556.2(HMMR):​c.462+21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,482,654 control chromosomes in the GnomAD database, including 81,992 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 0.39 (12812 hom., cov: 33)
  • Exomes 𝑓: 0.31 (69180 hom.)
• Consequence: HMMR NM_001142556.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMMR	NM_001142556.2	c.462+21T>C		intron_variant		ENST00000393915.9	NP_001136028.1
HMMR	NM_012484.3	c.459+21T>C		intron_variant			NP_036616.2
HMMR	NM_012485.3	c.414+21T>C		intron_variant			NP_036617.2
HMMR	NM_001142557.2	c.201+21T>C		intron_variant			NP_001136029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMMR	ENST00000393915.9	c.462+21T>C		intron_variant		1	NM_001142556.2	ENSP00000377492.4
HMMR	ENST00000520345.5	c.117+21T>C		intron_variant		2		ENSP00000428481.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59505 AN: 152010 Hom.: 12785 Cov.: 33

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.341

GnomAD3 exomes AF: 0.353 AC: 82195 AN: 232668 Hom.: 15560 AF XY: 0.344 AC XY: 43584 AN XY: 126602

Gnomad AFR exome AF: 0.576

Gnomad AMR exome AF: 0.383

Gnomad ASJ exome AF: 0.258

Gnomad EAS exome AF: 0.556

Gnomad SAS exome AF: 0.298

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.304

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.314 AC: 417622 AN: 1330528 Hom.: 69180 Cov.: 18 AF XY: 0.312 AC XY: 208421 AN XY: 667786

Gnomad4 AFR exome AF: 0.574

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.568

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.358

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.392 AC: 59580 AN: 152126 Hom.: 12812 Cov.: 33 AF XY: 0.394 AC XY: 29269 AN XY: 74360

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.350

Alfa AF: 0.316 Hom.: 4264

Bravo AF: 0.400

Asia WGS AF: 0.433 AC: 1503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs299283; hg19: chr5-162896856; COSMIC: COSV62374143; COSMIC: COSV62374143;