Variant 10-90743643-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019859.4(HTR7):c.1343C>G(p.Pro448Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 1,613,886 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P448Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.018 ( 56 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 79 hom. )

Consequence

HTR7
NM_019859.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.12

Variant links:

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]

HTR7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002271235).

BP6

Variant 10-90743643-G-C is Benign according to our data. Variant chr10-90743643-G-C is described in ClinVar as [Benign]. Clinvar id is 778468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HTR7	NM_019859.4 linkuse as main transcript	c.1343C>G	p.Pro448Arg	missense_variant	3/4	ENST00000336152.8
HTR7	XM_024447973.2 linkuse as main transcript	c.749C>G	p.Pro250Arg	missense_variant	3/4
HTR7	NM_000872.5 linkuse as main transcript	c.1296-1115C>G		intron_variant
HTR7	NM_019860.4 linkuse as main transcript	c.*2-1115C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR7	ENST00000336152.8 linkuse as main transcript	c.1343C>G	p.Pro448Arg	missense_variant	3/4	1	NM_019859.4		P34969-1
HTR7	ENST00000277874.10 linkuse as main transcript	c.1296-1115C>G		intron_variant		1		A1	P34969-2
HTR7	ENST00000371719.2 linkuse as main transcript	c.*2-1115C>G		intron_variant		1		P4	P34969-3

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2670

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00911

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00769

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00391

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00741

AC:

1862

AN:

251380

Hom.:

AF XY:

0.00669

AC XY:

909

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.0509

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.0326

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00470

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00332

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00542

AC:

7923

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00530

AC XY:

3851

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.0522

Gnomad4 AMR exome

AF:

0.00483

Gnomad4 ASJ exome

AF:

0.0298

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.00472

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00374

Gnomad4 OTH exome

AF:

0.00898

GnomAD4 genome

AF:

0.0176

AC:

2673

AN:

152198

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1234

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0499

Gnomad4 AMR

AF:

0.00910

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00748

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00391

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00558

Hom.:

Bravo

AF:

0.0193

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.0490

AC:

216

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00826

AC:

1003

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.0060

DANN

Benign

0.20

DEOGEN2

Benign

0.12

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.00062

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.28

REVEL

Benign

0.026

Sift

Benign

0.46

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.089

MVP

0.47

MPC

0.44

ClinPred

0.00064

GERP RS

-3.8

Varity_R

0.033

gMVP

0.11

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over