chr7-155084202-C-T

Variant names:

• chr7-155084202-C-T
• rs145552975
• NM_024012.4:c.789C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_024012.4(HTR5A):​c.789C>T​(p.His263His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000554 in 1,613,762 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (1 hom.)
• Consequence: HTR5A NM_024012.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.88
• Publications: 1 publications found

Genes affected

HTR5A (HGNC:5300): (5-hydroxytryptamine receptor 5A) The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects. The gene described in this record is a member of 5-hydroxytryptamine (serotonin) receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to G-proteins. This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 7-155084202-C-T is Benign according to our data. Variant chr7-155084202-C-T is described in ClinVar as Benign. ClinVar VariationId is 786553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.88 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024012.4. 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
	HTR5A	NM_024012.4	MANE Select	c.789C>T	p.His263His	synonymous	Exon 2 of 2	NP_076917.1	A4D2N2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR5A	ENST00000287907.3	TSL:1 MANE Select	c.789C>T	p.His263His	synonymous	Exon 2 of 2	ENSP00000287907.2	P47898
	HTR5A	ENST00000486819.1	TSL:1	n.145C>T		non_coding_transcript_exon	Exon 2 of 2
	HTR5A	ENST00000649716.1		n.*258C>T		non_coding_transcript_exon	Exon 3 of 3	ENSP00000497222.1	A0A3B3ISH0

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 293 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00464

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.000644 AC: 161 AN: 250176 AF XY: 0.000525

Gnomad AFR exome AF: 0.00480

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000222

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000411 AC: 601 AN: 1461554 Hom.: 1 Cov.: 32 AF XY: 0.000378 AC XY: 275 AN XY: 727092

African (AFR) AF: 0.00472 AC: 158 AN: 33476

American (AMR) AF: 0.00165 AC: 74 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53270

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5764

European-Non Finnish (NFE) AF: 0.000260 AC: 289 AN: 1111896

Other (OTH) AF: 0.00106 AC: 64 AN: 60388

GnomAD4 genome AF: 0.00193 AC: 293 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.00194 AC XY: 144 AN XY: 74410

African (AFR) AF: 0.00462 AC: 192 AN: 41536

American (AMR) AF: 0.00347 AC: 53 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68008

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00108 Hom.: 1

Bravo AF: 0.00232

EpiCase AF: 0.000709

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.20
DANN	Benign	0.55
PhyloP100		-1.9
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: rs145552975; hg19: chr7-154875912; COSMIC: COSV105159184;