rs2901127

chr10-90835309-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.539+21824G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,116 control chromosomes in the GnomAD database, including 1,062 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 0.11 (1062 hom., cov: 32)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935

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 (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR7	NM_019859.4	c.539+21824G>A		intron_variant		ENST00000336152.8
HTR7	NM_000872.5	c.539+21824G>A		intron_variant
HTR7	NM_019860.4	c.539+21824G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR7	ENST00000336152.8	c.539+21824G>A		intron_variant		1	NM_019859.4
HTR7	ENST00000277874.10	c.539+21824G>A		intron_variant		1		A1
HTR7	ENST00000371719.2	c.539+21824G>A		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16169 AN: 151998 Hom.: 1061 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0949

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.0938

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

GnomAD4 genome AF: 0.106 AC: 16186 AN: 152116 Hom.: 1062 Cov.: 32 AF XY: 0.106 AC XY: 7859 AN XY: 74370

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0741

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.0939

Gnomad4 FIN AF: 0.0965

Gnomad4 NFE AF: 0.0730

Gnomad4 OTH AF: 0.0947

Alfa AF: 0.0776 Hom.: 686

Bravo AF: 0.109

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.2
Dann	Benign	0.39

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: rs2901127; hg19: chr10-92595066;