chr10-90745647-G-A

Variant names:

• chr10-90745647-G-A
• rs1935347
• NM_019859.4:c.1296-1957C>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.1296-1957C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,164 control chromosomes in the GnomAD database, including 31,279 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 0.62 (31279 hom., cov: 33)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR7	NM_019859.4	c.1296-1957C>T		intron_variant	Intron 2 of 3	ENST00000336152.8	NP_062873.1
HTR7	NM_000872.5	c.1296-3119C>T		intron_variant	Intron 2 of 2		NP_000863.1
HTR7	NM_019860.4	c.*2-3119C>T		intron_variant	Intron 2 of 2		NP_062874.1
HTR7	XM_024447973.2	c.702-1957C>T		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.1296-1957C>T		intron_variant	Intron 2 of 3	1	NM_019859.4	ENSP00000337949.3
HTR7	ENST00000277874.10	c.1296-3119C>T		intron_variant	Intron 2 of 2	1		ENSP00000277874.6
HTR7	ENST00000371719.2	c.*2-3119C>T		intron_variant	Intron 2 of 2	1		ENSP00000360784.2

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94464 AN: 152046 Hom.: 31226 Cov.: 33

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.622 AC: 94577 AN: 152164 Hom.: 31279 Cov.: 33 AF XY: 0.620 AC XY: 46113 AN XY: 74354

African (AFR) AF: 0.868 AC: 36076 AN: 41568

American (AMR) AF: 0.534 AC: 8160 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1793 AN: 3464

East Asian (EAS) AF: 0.685 AC: 3548 AN: 5178

South Asian (SAS) AF: 0.602 AC: 2903 AN: 4824

European-Finnish (FIN) AF: 0.520 AC: 5484 AN: 10550

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34756 AN: 67986

Other (OTH) AF: 0.591 AC: 1245 AN: 2106

Alfa AF: 0.558 Hom.: 14518

Bravo AF: 0.633

Asia WGS AF: 0.646 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.5
DANN	Benign	0.45
PhyloP100		0.55
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: rs1935347; hg19: chr10-92505404;