rs11812708

Positions:

• chr10-90745508-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019859.4(HTR7):​c.1296-1818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,170 control chromosomes in the GnomAD database, including 4,315 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 0.23 (4315 hom., cov: 32)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198

Genes affected

HTR7 (HGNC:5302): (5-hydroxytryptamine receptor 7) The neurotransmitter, serotonin, is thought to play a role in various cognitive and behavioral functions. The serotonin receptor encoded by this gene belongs to the superfamily of G protein-coupled receptors and the gene is a candidate locus for involvement in autistic disorder and other neuropsychiatric disorders. Three splice variants have been identified which encode proteins that differ in the length of their carboxy terminal ends. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR7	NM_019859.4	c.1296-1818A>G		intron_variant		ENST00000336152.8	NP_062873.1
HTR7	NM_000872.5	c.1296-2980A>G		intron_variant			NP_000863.1
HTR7	NM_019860.4	c.*2-2980A>G		intron_variant			NP_062874.1
HTR7	XM_024447973.2	c.702-1818A>G		intron_variant			XP_024303741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR7	ENST00000336152.8	c.1296-1818A>G		intron_variant		1	NM_019859.4	ENSP00000337949
HTR7	ENST00000277874.10	c.1296-2980A>G		intron_variant		1		ENSP00000277874	A1
HTR7	ENST00000371719.2	c.*2-2980A>G		intron_variant		1		ENSP00000360784	P4

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35096 AN: 152052 Hom.: 4309 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.230

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.231 AC: 35128 AN: 152170 Hom.: 4315 Cov.: 32 AF XY: 0.230 AC XY: 17109 AN XY: 74394

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.228

Alfa AF: 0.204 Hom.: 4348

Bravo AF: 0.238

Asia WGS AF: 0.188 AC: 651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs11812708; hg19: chr10-92505265;