rs6298

Variant names:

• chr6-77463275-G-A
• rs6298
• NM_000863.3:c.129C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-77463275-G-A
• chr6-77463275-G-C
• chr6-77463275-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000863.3(HTR1B):​c.129C>T​(p.Ser43Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,613,886 control chromosomes in the GnomAD database, including 64,085 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 0.27 (6051 hom., cov: 32)
  • Exomes 𝑓: 0.28 (58034 hom.)
• Consequence: HTR1B NM_000863.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.588
• Publications: 66 publications found

Genes affected

HTR1B (HGNC:5287): (5-hydroxytryptamine receptor 1B) The protein encoded by this intronless gene is a G-protein coupled receptor for serotonin (5-hydroxytryptamine). Ligand binding activates second messengers that inhibit the activity of adenylate cyclase and manage the release of serotonin, dopamine, and acetylcholine in the brain. The encoded protein may be involved in several neuropsychiatric disorders and therefore is often a target of antidepressant and other psychotherapeutic drugs. [provided by RefSeq, Nov 2015]

LOC105377864 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=0.588 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR1B	NM_000863.3	c.129C>T	p.Ser43Ser	synonymous_variant	Exon 1 of 1	ENST00000369947.5	NP_000854.1
LOC105377864	XM_047419659.1	c.-11184G>A		5_prime_UTR_variant	Exon 2 of 6		XP_047275615.1
LOC105377864	XM_047419660.1	c.-3742-11251G>A		intron_variant	Intron 5 of 8		XP_047275616.1
LOC105377864	XM_047419661.1	c.-3917+157G>A		intron_variant	Intron 1 of 5		XP_047275617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR1B	ENST00000369947.5	c.129C>T	p.Ser43Ser	synonymous_variant	Exon 1 of 1	6	NM_000863.3	ENSP00000358963.3
ENSG00000296734	ENST00000741460.1	n.48+3625C>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41737 AN: 152016 Hom.: 6055 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.273

GnomAD2 exomes AF: 0.312 AC: 78496 AN: 251480 AF XY: 0.310

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.431

Gnomad ASJ exome AF: 0.249

Gnomad EAS exome AF: 0.500

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.277 AC: 404461 AN: 1461752 Hom.: 58034 Cov.: 38 AF XY: 0.278 AC XY: 202181 AN XY: 727184

African (AFR) AF: 0.230 AC: 7687 AN: 33478

American (AMR) AF: 0.426 AC: 19051 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 6515 AN: 26134

East Asian (EAS) AF: 0.476 AC: 18896 AN: 39700

South Asian (SAS) AF: 0.354 AC: 30528 AN: 86254

European-Finnish (FIN) AF: 0.252 AC: 13480 AN: 53420

Middle Eastern (MID) AF: 0.255 AC: 1469 AN: 5766

European-Non Finnish (NFE) AF: 0.261 AC: 289726 AN: 1111888

Other (OTH) AF: 0.283 AC: 17109 AN: 60388

GnomAD4 genome AF: 0.274 AC: 41747 AN: 152134 Hom.: 6051 Cov.: 32 AF XY: 0.279 AC XY: 20727 AN XY: 74378

African (AFR) AF: 0.233 AC: 9662 AN: 41516

American (AMR) AF: 0.380 AC: 5818 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3470

East Asian (EAS) AF: 0.496 AC: 2558 AN: 5154

South Asian (SAS) AF: 0.348 AC: 1674 AN: 4812

European-Finnish (FIN) AF: 0.244 AC: 2583 AN: 10606

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17630 AN: 67966

Other (OTH) AF: 0.274 AC: 579 AN: 2112

Alfa AF: 0.265 Hom.: 16211

Bravo AF: 0.283

Asia WGS AF: 0.395 AC: 1369 AN: 3478

EpiCase AF: 0.263

EpiControl AF: 0.256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.5
DANN	Benign	0.73
PhyloP100		0.59
PromoterAI		-0.025	Neutral
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: rs6298; hg19: chr6-78172992; COSMIC: COSV64051193;