rs56109847

Variant names:

• chr3-184106769-G-A
• rs56109847
• NM_001256613.2:c.*76G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001256613.2(HTR3E):​c.*76G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,423,154 control chromosomes in the GnomAD database, including 1,254 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 0.028 (84 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1170 hom.)
• Consequence: HTR3E NM_001256613.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 38 publications found

Genes affected

HTR3E (HGNC:24005): (5-hydroxytryptamine receptor 3E) This locus encodes a 5-hydroxytryptamine (serotonin) receptor subunit. The encoded protein, subunit E, may play a role in neurotransmission in myenteric neurons. Genes encoding subunits C, D and E form a cluster on chromosome 3. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Feb 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0283 (4309/152178) while in subpopulation NFE AF = 0.0448 (3045/67994). AF 95% confidence interval is 0.0435. There are 84 homozygotes in GnomAd4. There are 2007 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 84 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256613.2. 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
	HTR3E	NM_001256613.2	MANE Select	c.*76G>A		3_prime_UTR	Exon 9 of 9	NP_001243542.1	A5X5Y0-1
	HTR3E	NM_001256614.1		c.*76G>A		3_prime_UTR	Exon 7 of 7	NP_001243543.1	A5X5Y0-6
	HTR3E	NM_182589.2		c.*76G>A		3_prime_UTR	Exon 8 of 8	NP_872395.2	A5X5Y0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3E	ENST00000415389.6	TSL:1 MANE Select	c.*76G>A		3_prime_UTR	Exon 9 of 9	ENSP00000401444.2	A5X5Y0-1
	HTR3E	ENST00000335304.6	TSL:1	c.*76G>A		3_prime_UTR	Exon 8 of 8	ENSP00000335511.2	A5X5Y0-3
	HTR3E	ENST00000440596.2	TSL:1	c.*76G>A		downstream_gene	N/A	ENSP00000406050.2	A5X5Y0-6

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4312 AN: 152060 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.00843

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0448

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.0402 AC: 51145 AN: 1270976 Hom.: 1170 Cov.: 19 AF XY: 0.0397 AC XY: 25336 AN XY: 637704

African (AFR) AF: 0.00690 AC: 200 AN: 28992

American (AMR) AF: 0.0129 AC: 513 AN: 39722

Ashkenazi Jewish (ASJ) AF: 0.0117 AC: 259 AN: 22194

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38776

South Asian (SAS) AF: 0.0179 AC: 1360 AN: 76006

European-Finnish (FIN) AF: 0.0353 AC: 1824 AN: 51628

Middle Eastern (MID) AF: 0.00343 AC: 18 AN: 5252

European-Non Finnish (NFE) AF: 0.0474 AC: 45242 AN: 954654

Other (OTH) AF: 0.0321 AC: 1728 AN: 53752

GnomAD4 genome AF: 0.0283 AC: 4309 AN: 152178 Hom.: 84 Cov.: 32 AF XY: 0.0270 AC XY: 2007 AN XY: 74376

African (AFR) AF: 0.00840 AC: 349 AN: 41532

American (AMR) AF: 0.0194 AC: 297 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0129 AC: 62 AN: 4810

European-Finnish (FIN) AF: 0.0344 AC: 364 AN: 10584

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0448 AC: 3045 AN: 67994

Other (OTH) AF: 0.0326 AC: 69 AN: 2114

Alfa AF: 0.0234 Hom.: 20

Bravo AF: 0.0257

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.37
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism

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: rs56109847; hg19: chr3-183824557;