10-90817174-T-C

Position:

• chr10-90817174-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.539+39959A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,958 control chromosomes in the GnomAD database, including 31,846 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 0.63 (31846 hom., cov: 31)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR7	NM_019859.4	c.539+39959A>G		intron_variant		ENST00000336152.8	NP_062873.1
HTR7	NM_000872.5	c.539+39959A>G		intron_variant			NP_000863.1
HTR7	NM_019860.4	c.539+39959A>G		intron_variant			NP_062874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR7	ENST00000336152.8	c.539+39959A>G		intron_variant		1	NM_019859.4	ENSP00000337949
HTR7	ENST00000277874.10	c.539+39959A>G		intron_variant		1		ENSP00000277874	A1
HTR7	ENST00000371719.2	c.539+39959A>G		intron_variant		1		ENSP00000360784	P4

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95752 AN: 151840 Hom.: 31791 Cov.: 31

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.631 AC: 95868 AN: 151958 Hom.: 31846 Cov.: 31 AF XY: 0.629 AC XY: 46676 AN XY: 74256

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.604

Alfa AF: 0.587 Hom.: 3378

Bravo AF: 0.641

Asia WGS AF: 0.633 AC: 2200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.40

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: rs7082558; hg19: chr10-92576931;