chr20-62216348-C-T

Variant names:

• chr20-62216348-C-T
• rs3787429
• NM_007232.3:c.996G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007232.3(HRH3):​c.996G>A​(p.Ser332Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,592,330 control chromosomes in the GnomAD database, including 136,962 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 0.45 (15747 hom., cov: 33)
  • Exomes 𝑓: 0.41 (121215 hom.)
• Consequence: HRH3 NM_007232.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 23 publications found

Genes affected

HRH3 (HGNC:5184): (histamine receptor H3) Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3 and H4. This gene encodes one of the histamine receptors (H3) which belongs to the family 1 of G protein-coupled receptors. It is an integral membrane protein and can regulate neurotransmitter release. This receptor can also increase voltage-dependent calcium current in smooth muscles and innervates the blood vessels and the heart in cardiovascular system. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.982573E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007232.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH3	NM_007232.3	MANE Select	c.996G>A	p.Ser332Ser	synonymous	Exon 3 of 3	NP_009163.2	Q9Y5N1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH3	ENST00000340177.10	TSL:1 MANE Select	c.996G>A	p.Ser332Ser	synonymous	Exon 3 of 3	ENSP00000342560.5	Q9Y5N1-1
	HRH3	ENST00000317393.10	TSL:1	c.822-66G>A		intron	N/A	ENSP00000321482.7	A0A0A0MR48
	HRH3	ENST00000932927.1		c.954G>A	p.Ser318Ser	synonymous	Exon 3 of 3	ENSP00000602986.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68060 AN: 151942 Hom.: 15713 Cov.: 33

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.417

GnomAD2 exomes AF: 0.447 AC: 98502 AN: 220444 AF XY: 0.443

Gnomad AFR exome AF: 0.573

Gnomad AMR exome AF: 0.548

Gnomad ASJ exome AF: 0.375

Gnomad EAS exome AF: 0.340

Gnomad FIN exome AF: 0.425

Gnomad NFE exome AF: 0.400

Gnomad OTH exome AF: 0.423

GnomAD4 exome AF: 0.407 AC: 586049 AN: 1440268 Hom.: 121215 Cov.: 62 AF XY: 0.410 AC XY: 292354 AN XY: 713928

African (AFR) AF: 0.561 AC: 18515 AN: 33002

American (AMR) AF: 0.538 AC: 22749 AN: 42322

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 9657 AN: 25796

East Asian (EAS) AF: 0.330 AC: 12710 AN: 38530

South Asian (SAS) AF: 0.524 AC: 44194 AN: 84262

European-Finnish (FIN) AF: 0.419 AC: 21246 AN: 50750

Middle Eastern (MID) AF: 0.378 AC: 2119 AN: 5602

European-Non Finnish (NFE) AF: 0.391 AC: 430748 AN: 1100490

Other (OTH) AF: 0.405 AC: 24111 AN: 59514

GnomAD4 genome AF: 0.448 AC: 68148 AN: 152062 Hom.: 15747 Cov.: 33 AF XY: 0.449 AC XY: 33382 AN XY: 74330

African (AFR) AF: 0.555 AC: 23006 AN: 41468

American (AMR) AF: 0.470 AC: 7193 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1236 AN: 3472

East Asian (EAS) AF: 0.343 AC: 1772 AN: 5160

South Asian (SAS) AF: 0.531 AC: 2557 AN: 4816

European-Finnish (FIN) AF: 0.418 AC: 4427 AN: 10596

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26644 AN: 67944

Other (OTH) AF: 0.416 AC: 876 AN: 2108

Alfa AF: 0.405 Hom.: 21297

Bravo AF: 0.456

TwinsUK AF: 0.389 AC: 1444

ALSPAC AF: 0.390 AC: 1502

ESP6500AA AF: 0.547 AC: 2403

ESP6500EA AF: 0.395 AC: 3387

ExAC AF: 0.426 AC: 51112

Asia WGS AF: 0.481 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.21
DANN	Benign	0.80
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0000080	T
PhyloP100		-1.9
Vest4		0.050
GERP RS		-9.2
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: rs3787429; hg19: chr20-60791404; COSMIC: COSV58047736;