rs1935351

Variant names:

• chr10-90805968-C-T
• rs1935351
• NM_019859.4:c.539+51165G>A

Variant summary

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

The NM_019859.4(HTR7):​c.539+51165G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,852 control chromosomes in the GnomAD database, including 6,319 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 0.28 (6319 hom., cov: 32)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR7	NM_019859.4	c.539+51165G>A		intron_variant	Intron 1 of 3	ENST00000336152.8	NP_062873.1
HTR7	NM_000872.5	c.539+51165G>A		intron_variant	Intron 1 of 2		NP_000863.1
HTR7	NM_019860.4	c.539+51165G>A		intron_variant	Intron 1 of 2		NP_062874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR7	ENST00000336152.8	c.539+51165G>A		intron_variant	Intron 1 of 3	1	NM_019859.4	ENSP00000337949.3
HTR7	ENST00000277874.10	c.539+51165G>A		intron_variant	Intron 1 of 2	1		ENSP00000277874.6
HTR7	ENST00000371719.2	c.539+51165G>A		intron_variant	Intron 1 of 2	1		ENSP00000360784.2

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41869 AN: 151734 Hom.: 6306 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.276 AC: 41915 AN: 151852 Hom.: 6319 Cov.: 32 AF XY: 0.276 AC XY: 20481 AN XY: 74200

African (AFR) AF: 0.404 AC: 16717 AN: 41382

American (AMR) AF: 0.284 AC: 4328 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1451 AN: 5172

South Asian (SAS) AF: 0.282 AC: 1355 AN: 4800

European-Finnish (FIN) AF: 0.180 AC: 1892 AN: 10518

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14572 AN: 67930

Other (OTH) AF: 0.265 AC: 559 AN: 2112

Alfa AF: 0.254 Hom.: 862

Bravo AF: 0.288

Asia WGS AF: 0.260 AC: 901 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.22
PhyloP100		0.17
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: rs1935351; hg19: chr10-92565725;