rs762544665

Variant names:

• chr6-47009097-G-A
• rs762544665
• NM_153840.4:c.2338C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153840.4(ADGRF1):​c.2338C>T​(p.Arg780Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R780Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: ADGRF1 NM_153840.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.471
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16598183).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153840.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRF1	NM_153840.4	MANE Select	c.2338C>T	p.Arg780Trp	missense	Exon 11 of 15	NP_722582.2	Q5T601-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRF1	ENST00000371253.7	TSL:1 MANE Select	c.2338C>T	p.Arg780Trp	missense	Exon 11 of 15	ENSP00000360299.2	Q5T601-1
	ADGRF1	ENST00000283297.5	TSL:1	c.1747C>T	p.Arg583Trp	missense	Exon 5 of 9	ENSP00000283297.5	A0A0C4DH10
	ADGRF1	ENST00000449332.6	TSL:1	n.2309C>T		non_coding_transcript_exon	Exon 9 of 13

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 251076 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000246 AC: 36 AN: 1461820 Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111992

Other (OTH) AF: 0.0000662 AC: 4 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000660 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.47
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.046
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.99	D
Vest4		0.21
MutPred		0.47		Loss of disorder (P = 0.0016)
MVP		0.45
MPC		0.28
ClinPred		0.43	T
GERP RS		2.9
Varity_R		0.12
gMVP		0.35
Mutation Taster		=96/4	polymorphism

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: rs762544665; hg19: chr6-46976833; COSMIC: COSV105107196; COSMIC: COSV105107196;