Genetic Variant ADGRF1:p.Asp813His (chr6-47008998-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_153840.4(ADGRF1):c.2437G>C(p.Asp813His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,612,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ADGRF1
NM_153840.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0850

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28570634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRF1	NM_153840.4 link	c.2437G>C	p.Asp813His	missense_variant	Exon 11 of 15	ENST00000371253.7	NP_722582.2	Q5T601-1
ADGRF1	XM_047418639.1 link	c.1849G>C	p.Asp617His	missense_variant	Exon 5 of 9		XP_047274595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADGRF1	ENST00000371253.7 link	c.2437G>C	p.Asp813His	missense_variant	Exon 11 of 15	1	NM_153840.4	ENSP00000360299.2	Q5T601-1
ADGRF1	ENST00000283297.5 link	c.1846G>C	p.Asp616His	missense_variant	Exon 5 of 9	1		ENSP00000283297.5	A0A0C4DH10
ADGRF1	ENST00000449332.6 link	n.2408G>C		non_coding_transcript_exon_variant	Exon 9 of 13	1
ADGRF1	ENST00000419892.6 link	n.8703G>C		non_coding_transcript_exon_variant	Exon 9 of 13	2

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000320

AC:

AN:

250376

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135248

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1460120

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726034

show subpopulations

Gnomad4 AFR exome

AF:

0.000688

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000138

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2437G>C (p.D813H) alteration is located in exon 11 (coding exon 10) of the ADGRF1 gene. This alteration results from a G to C substitution at nucleotide position 2437, causing the aspartic acid (D) at amino acid position 813 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

T;T

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.89

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.17

Sift

Benign

0.031

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

1.0

D;.

Vest4

0.59

MVP

0.53

MPC

0.34

ClinPred

0.69

GERP RS

4.1

Varity_R

0.16

gMVP

0.34

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