rs12761105

Positions:

• chr10-90853660-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+3473A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,940 control chromosomes in the GnomAD database, including 4,061 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 (4061 hom., cov: 31)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR7	NM_019859.4	c.539+3473A>G		intron_variant		ENST00000336152.8
HTR7	NM_000872.5	c.539+3473A>G		intron_variant
HTR7	NM_019860.4	c.539+3473A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR7	ENST00000336152.8	c.539+3473A>G		intron_variant		1	NM_019859.4
HTR7	ENST00000277874.10	c.539+3473A>G		intron_variant		1		A1
HTR7	ENST00000371719.2	c.539+3473A>G		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31338 AN: 151822 Hom.: 4053 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.206 AC: 31370 AN: 151940 Hom.: 4061 Cov.: 31 AF XY: 0.208 AC XY: 15436 AN XY: 74256

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.226

Alfa AF: 0.166 Hom.: 339

Bravo AF: 0.224

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.7
DANN	Benign	0.83

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: rs12761105; hg19: chr10-92613417;