rs10509608

chr10-90744297-A-Gchr10-90744297-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• 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/exons	MANE	UniProt
HTR7	NM_019859.4	c.1296-607T>C		intron_variant		ENST00000336152.8
HTR7	NM_000872.5	c.1296-1769T>C		intron_variant
HTR7	NM_019860.4	c.*2-1769T>C		intron_variant
HTR7	XM_024447973.2	c.702-607T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR7	ENST00000336152.8	c.1296-607T>C		intron_variant		1	NM_019859.4
HTR7	ENST00000277874.10	c.1296-1769T>C		intron_variant		1		A1
HTR7	ENST00000371719.2	c.*2-1769T>C		intron_variant		1		P4

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

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.202

Alfa AF: 0.118 Hom.: 242

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

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: rs10509608; hg19: chr10-92504054;