rs12412496

Variant names:

• chr10-90786408-G-A
• rs12412496
• NM_019859.4:c.540-36814C>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.540-36814C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,026 control chromosomes in the GnomAD database, including 5,488 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 0.26 (5488 hom., cov: 32)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452
• Publications: 8 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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR7	NM_019859.4	c.540-36814C>T		intron_variant	Intron 1 of 3	ENST00000336152.8	NP_062873.1
HTR7	NM_000872.5	c.540-36814C>T		intron_variant	Intron 1 of 2		NP_000863.1
HTR7	NM_019860.4	c.540-36814C>T		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.540-36814C>T		intron_variant	Intron 1 of 3	1	NM_019859.4	ENSP00000337949.3
HTR7	ENST00000277874.10	c.540-36814C>T		intron_variant	Intron 1 of 2	1		ENSP00000277874.6
HTR7	ENST00000371719.2	c.540-36814C>T		intron_variant	Intron 1 of 2	1		ENSP00000360784.2

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39521 AN: 151908 Hom.: 5477 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.260 AC: 39558 AN: 152026 Hom.: 5488 Cov.: 32 AF XY: 0.261 AC XY: 19381 AN XY: 74316

African (AFR) AF: 0.350 AC: 14506 AN: 41440

American (AMR) AF: 0.275 AC: 4204 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1443 AN: 5164

South Asian (SAS) AF: 0.281 AC: 1355 AN: 4826

European-Finnish (FIN) AF: 0.180 AC: 1906 AN: 10570

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14573 AN: 67978

Other (OTH) AF: 0.255 AC: 537 AN: 2110

Alfa AF: 0.242 Hom.: 605

Bravo AF: 0.271

Asia WGS AF: 0.258 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.45
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: rs12412496; hg19: chr10-92546165; COSMIC: COSV53282508;