rs130060

Variant names:

• chr6-77463033-A-C
• rs130060
• NM_000863.3:c.371T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-77463033-A-C
• chr6-77463033-A-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000369947.5(HTR1B):​c.371T>G​(p.Phe124Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,614,186 control chromosomes in the GnomAD database, including 170 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 0.0091 (7 hom., cov: 32)
  • Exomes 𝑓: 0.013 (163 hom.)
• Consequence: HTR1B ENST00000369947.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32
• Publications: 27 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012479603).
• BS2: High AC in GnomAd4 at 1387 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369947.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR1B	NM_000863.3	MANE Select	c.371T>G	p.Phe124Cys	missense	Exon 1 of 1	NP_000854.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR1B	ENST00000369947.5	TSL:6 MANE Select	c.371T>G	p.Phe124Cys	missense	Exon 1 of 1	ENSP00000358963.3
	ENSG00000296734	ENST00000741460.1		n.48+3867T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00911 AC: 1386 AN: 152200 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00372

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00994 AC: 2498 AN: 251286 AF XY: 0.00991

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00885

Gnomad ASJ exome AF: 0.0149

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00924

Gnomad NFE exome AF: 0.0137

Gnomad OTH exome AF: 0.0124

GnomAD4 exome AF: 0.0131 AC: 19138 AN: 1461868 Hom.: 163 Cov.: 38 AF XY: 0.0128 AC XY: 9305 AN XY: 727236

African (AFR) AF: 0.00212 AC: 71 AN: 33480

American (AMR) AF: 0.00874 AC: 391 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 415 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.00654 AC: 564 AN: 86256

European-Finnish (FIN) AF: 0.00908 AC: 485 AN: 53398

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5768

European-Non Finnish (NFE) AF: 0.0148 AC: 16451 AN: 1112010

Other (OTH) AF: 0.0122 AC: 736 AN: 60396

GnomAD4 genome AF: 0.00911 AC: 1387 AN: 152318 Hom.: 7 Cov.: 32 AF XY: 0.00827 AC XY: 616 AN XY: 74484

African (AFR) AF: 0.00214 AC: 89 AN: 41582

American (AMR) AF: 0.0103 AC: 158 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5162

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4832

European-Finnish (FIN) AF: 0.00706 AC: 75 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0142 AC: 969 AN: 68026

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.0124 Hom.: 59

Bravo AF: 0.00908

TwinsUK AF: 0.0116 AC: 43

ALSPAC AF: 0.0117 AC: 45

ESP6500AA AF: 0.00363 AC: 16

ESP6500EA AF: 0.0135 AC: 116

ExAC AF: 0.00925 AC: 1123

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0142

EpiControl AF: 0.0139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.86	D
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		9.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.67	P
Vest4		0.56
MVP		0.44
MPC		1.5
ClinPred		0.033	T
GERP RS		5.3
PromoterAI		-0.024	Neutral
Varity_R		0.38
gMVP		0.71
Mutation Taster		=56/44	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: rs130060; hg19: chr6-78172750; COSMIC: COSV105286209;