rs11186299

chr10-90753586-C-Achr10-90753586-C-T

Variant summary

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

The NM_019859.4(HTR7):c.540-3992G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 152,132 control chromosomes in the GnomAD database, including 345 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 0.058 (345 hom., cov: 33)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR7	NM_019859.4	c.540-3992G>T		intron_variant		ENST00000336152.8
HTR7	NM_000872.5	c.540-3992G>T		intron_variant
HTR7	NM_019860.4	c.540-3992G>T		intron_variant
HTR7	XM_024447973.2	c.-55-3992G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR7	ENST00000336152.8	c.540-3992G>T		intron_variant		1	NM_019859.4
HTR7	ENST00000277874.10	c.540-3992G>T		intron_variant		1		A1
HTR7	ENST00000371719.2	c.540-3992G>T		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8782 AN: 152016 Hom.: 346 Cov.: 33

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.0994

Gnomad FIN AF: 0.0946

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0719

Gnomad OTH AF: 0.0592

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

GnomAD4 genome AF: 0.0577 AC: 8773 AN: 152132 Hom.: 345 Cov.: 33 AF XY: 0.0595 AC XY: 4423 AN XY: 74356

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0544

Gnomad4 ASJ AF: 0.0306

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.0988

Gnomad4 FIN AF: 0.0946

Gnomad4 NFE AF: 0.0719

Gnomad4 OTH AF: 0.0595

Alfa AF: 0.0275 Hom.: 14

Bravo AF: 0.0525

Asia WGS AF: 0.122 AC: 423 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.54
Dann	Benign	0.47

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: rs11186299; hg19: chr10-92513343;