chr5-163478574-G-T

Position:

• chr5-163478574-G-T

Variant summary

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

The NM_001142556.2(HMMR):​c.1269-110G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 699,182 control chromosomes in the GnomAD database, including 18,825 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 0.18 (2998 hom., cov: 32)
  • Exomes 𝑓: 0.23 (15827 hom.)
• Consequence: HMMR NM_001142556.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMMR	NM_001142556.2	c.1269-110G>T		intron_variant		ENST00000393915.9	NP_001136028.1
HMMR	NM_012484.3	c.1266-110G>T		intron_variant			NP_036616.2
HMMR	NM_012485.3	c.1221-110G>T		intron_variant			NP_036617.2
HMMR	NM_001142557.2	c.1008-110G>T		intron_variant			NP_001136029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMMR	ENST00000393915.9	c.1269-110G>T		intron_variant		1	NM_001142556.2	ENSP00000377492.4
HMMR	ENST00000358715.3	c.1266-110G>T		intron_variant		1		ENSP00000351554.3
HMMR	ENST00000353866.7	c.1221-110G>T		intron_variant		1		ENSP00000185942.6
HMMR	ENST00000432118.6	c.1008-110G>T		intron_variant		2		ENSP00000402673.2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28133 AN: 152002 Hom.: 3002 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.229 AC: 125118 AN: 547062 Hom.: 15827 AF XY: 0.238 AC XY: 70209 AN XY: 295364

Gnomad4 AFR exome AF: 0.0956

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.185 AC: 28133 AN: 152120 Hom.: 2998 Cov.: 32 AF XY: 0.188 AC XY: 13994 AN XY: 74350

Gnomad4 AFR AF: 0.0929

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.209

Alfa AF: 0.192 Hom.: 745

Bravo AF: 0.178

Asia WGS AF: 0.282 AC: 983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.54

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: rs13183712; hg19: chr5-162905580; COSMIC: COSV62375590; COSMIC: COSV62375590;