rs10509608

Variant names:

• chr10-90744297-A-G
• rs10509608
• NM_019859.4:c.1296-607T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-90744297-A-G
• chr10-90744297-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019859.4(HTR7):​c.1296-607T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 149,440 control chromosomes in the GnomAD database, including 3,924 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 0.21 (3924 hom., cov: 27)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR7	NM_019859.4	c.1296-607T>C		intron_variant	Intron 2 of 3	ENST00000336152.8	NP_062873.1
HTR7	NM_000872.5	c.1296-1769T>C		intron_variant	Intron 2 of 2		NP_000863.1
HTR7	NM_019860.4	c.*2-1769T>C		intron_variant	Intron 2 of 2		NP_062874.1
HTR7	XM_024447973.2	c.702-607T>C		intron_variant	Intron 2 of 3		XP_024303741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR7	ENST00000336152.8	c.1296-607T>C		intron_variant	Intron 2 of 3	1	NM_019859.4	ENSP00000337949.3
HTR7	ENST00000277874.10	c.1296-1769T>C		intron_variant	Intron 2 of 2	1		ENSP00000277874.6
HTR7	ENST00000371719.2	c.*2-1769T>C		intron_variant	Intron 2 of 2	1		ENSP00000360784.2

Frequencies

GnomAD3 genomes AF: 0.207 AC: 30940 AN: 149322 Hom.: 3916 Cov.: 27

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.207 AC: 30983 AN: 149440 Hom.: 3924 Cov.: 27 AF XY: 0.206 AC XY: 15001 AN XY: 72774

African (AFR) AF: 0.345 AC: 13902 AN: 40308

American (AMR) AF: 0.182 AC: 2706 AN: 14870

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 482 AN: 3454

East Asian (EAS) AF: 0.307 AC: 1556 AN: 5076

South Asian (SAS) AF: 0.225 AC: 1043 AN: 4638

European-Finnish (FIN) AF: 0.112 AC: 1154 AN: 10340

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9595 AN: 67502

Other (OTH) AF: 0.202 AC: 414 AN: 2048

Alfa AF: 0.126 Hom.: 288

Bravo AF: 0.220

Asia WGS AF: 0.239 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.0
DANN	Benign	0.82
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs10509608; hg19: chr10-92504054;