10-90766173-G-C

Variant names:

• chr10-90766173-G-C
• rs12256352
• NM_019859.4:c.540-16579C>G

Variant summary

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

The NM_019859.4(HTR7):​c.540-16579C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,098 control chromosomes in the GnomAD database, including 1,588 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 0.12 (1588 hom., cov: 32)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 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.540-16579C>G		intron	N/A	NP_062873.1
	HTR7	NM_000872.5		c.540-16579C>G		intron	N/A	NP_000863.1
	HTR7	NM_019860.4		c.540-16579C>G		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.540-16579C>G		intron	N/A	ENSP00000337949.3
	HTR7	ENST00000277874.10	TSL:1	c.540-16579C>G		intron	N/A	ENSP00000277874.6
	HTR7	ENST00000371719.2	TSL:1	c.540-16579C>G		intron	N/A	ENSP00000360784.2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18615 AN: 151980 Hom.: 1582 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.123 AC: 18654 AN: 152098 Hom.: 1588 Cov.: 32 AF XY: 0.121 AC XY: 9006 AN XY: 74374

African (AFR) AF: 0.238 AC: 9852 AN: 41466

American (AMR) AF: 0.119 AC: 1821 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3466

East Asian (EAS) AF: 0.115 AC: 594 AN: 5174

South Asian (SAS) AF: 0.145 AC: 701 AN: 4822

European-Finnish (FIN) AF: 0.0187 AC: 198 AN: 10592

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4770 AN: 67982

Other (OTH) AF: 0.117 AC: 247 AN: 2106

Alfa AF: 0.100 Hom.: 139

Bravo AF: 0.134

Asia WGS AF: 0.110 AC: 382 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.1
DANN	Benign	0.59
PhyloP100		-0.056
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: rs12256352; hg19: chr10-92525930;