Variant 6-47009028-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000371253.7(ADGRF1):c.2407A>C(p.Thr803Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,614,014 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 22 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 15 hom. )

Consequence

ADGRF1
ENST00000371253.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.98

Variant links:

Genes affected

ADGRF1 (HGNC:18990): (adhesion G protein-coupled receptor F1) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within several processes, including memory; nervous system development; and positive regulation of CREB transcription factor activity. Predicted to be located in extracellular region and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ADGRF1 links:

ADGRF1 (HGNC:):

ADGRF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013400674).

BP6

Variant 6-47009028-T-G is Benign according to our data. Variant chr6-47009028-T-G is described in ClinVar as [Benign]. Clinvar id is 788994.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00729 (1110/152208) while in subpopulation AFR AF= 0.0243 (1011/41526). AF 95% confidence interval is 0.0231. There are 22 homozygotes in gnomad4. There are 497 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRF1	NM_153840.4 linkuse as main transcript	c.2407A>C	p.Thr803Pro	missense_variant	11/15	ENST00000371253.7	NP_722582.2	Q5T601-1
ADGRF1	XM_047418639.1 linkuse as main transcript	c.1819A>C	p.Thr607Pro	missense_variant	5/9		XP_047274595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADGRF1	ENST00000371253.7 linkuse as main transcript	c.2407A>C	p.Thr803Pro	missense_variant	11/15	1	NM_153840.4	ENSP00000360299.2	Q5T601-1
ADGRF1	ENST00000283297.5 linkuse as main transcript	c.1816A>C	p.Thr606Pro	missense_variant	5/9	1		ENSP00000283297.5	A0A0C4DH10
ADGRF1	ENST00000449332.6 linkuse as main transcript	n.2378A>C		non_coding_transcript_exon_variant	9/13	1
ADGRF1	ENST00000419892.6 linkuse as main transcript	n.8673A>C		non_coding_transcript_exon_variant	9/13	2

Frequencies

GnomAD3 genomes

AF:

0.00729

AC:

1109

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00249

AC:

624

AN:

250926

Hom.:

AF XY:

0.00203

AC XY:

275

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.0261

Gnomad AMR exome

AF:

0.00339

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000582

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00105

AC:

1539

AN:

1461806

Hom.:

Cov.:

AF XY:

0.000939

AC XY:

683

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0245

Gnomad4 AMR exome

AF:

0.00342

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000333

Gnomad4 OTH exome

AF:

0.00248

GnomAD4 genome

AF:

0.00729

AC:

1110

AN:

152208

Hom.:

Cov.:

AF XY:

0.00668

AC XY:

497

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0243

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00162

Hom.:

Bravo

AF:

0.00856

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0247

AC:

109

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00286

AC:

347

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.000763

EpiControl

AF:

0.000711

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

Labcorp Genetics (formerly Invitae), Labcorp

May 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.013

T;T

MetaSVM

Uncertain

-0.24

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-5.8

D;D

REVEL

Pathogenic

0.67

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.76

MVP

0.64

MPC

0.37

ClinPred

0.045

GERP RS

5.9

Varity_R

0.97

gMVP

0.86

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