10-90820837-A-G

Variant names:

• chr10-90820837-A-G
• rs1935350
• NM_019859.4:c.539+36296T>C

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+36296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,098 control chromosomes in the GnomAD database, including 4,459 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 (4459 hom., cov: 32)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR7	NM_019859.4	MANE Select	c.539+36296T>C		intron	N/A	NP_062873.1
	HTR7	NM_000872.5		c.539+36296T>C		intron	N/A	NP_000863.1
	HTR7	NM_019860.4		c.539+36296T>C		intron	N/A	NP_062874.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR7	ENST00000336152.8	TSL:1 MANE Select	c.539+36296T>C		intron	N/A	ENSP00000337949.3
	HTR7	ENST00000277874.10	TSL:1	c.539+36296T>C		intron	N/A	ENSP00000277874.6
	HTR7	ENST00000371719.2	TSL:1	c.539+36296T>C		intron	N/A	ENSP00000360784.2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32377 AN: 151980 Hom.: 4450 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.213 AC: 32408 AN: 152098 Hom.: 4459 Cov.: 32 AF XY: 0.214 AC XY: 15939 AN XY: 74366

African (AFR) AF: 0.381 AC: 15805 AN: 41432

American (AMR) AF: 0.225 AC: 3443 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 562 AN: 3472

East Asian (EAS) AF: 0.279 AC: 1445 AN: 5174

South Asian (SAS) AF: 0.234 AC: 1129 AN: 4816

European-Finnish (FIN) AF: 0.121 AC: 1288 AN: 10602

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8124 AN: 68002

Other (OTH) AF: 0.224 AC: 473 AN: 2110

Alfa AF: 0.157 Hom.: 312

Bravo AF: 0.231

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.72
PhyloP100		-0.28
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: rs1935350; hg19: chr10-92580594;