6-47009115-C-T

Position:

• chr6-47009115-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153840.4(ADGRF1):​c.2320G>A​(p.Val774Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADGRF1 NM_153840.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0550

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRF1	NM_153840.4	c.2320G>A	p.Val774Ile	missense_variant	11/15	ENST00000371253.7	NP_722582.2
ADGRF1	XM_047418639.1	c.1732G>A	p.Val578Ile	missense_variant	5/9		XP_047274595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRF1	ENST00000371253.7	c.2320G>A	p.Val774Ile	missense_variant	11/15	1	NM_153840.4	ENSP00000360299	P1
ADGRF1	ENST00000283297.5	c.1729G>A	p.Val577Ile	missense_variant	5/9	1		ENSP00000283297
ADGRF1	ENST00000449332.6	n.2291G>A		non_coding_transcript_exon_variant	9/13	1
ADGRF1	ENST00000419892.6	n.8586G>A		non_coding_transcript_exon_variant	9/13	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.2320G>A (p.V774I) alteration is located in exon 11 (coding exon 10) of the ADGRF1 gene. This alteration results from a G to A substitution at nucleotide position 2320, causing the valine (V) at amino acid position 774 to be replaced by an isoleucine (I). 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	0.077
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.1
DANN	Benign	0.19
DEOGEN2	Benign	0.0027	T;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.20	N;N
REVEL	Benign	0.075
Sift	Benign	1.0	T;T
Sift4G	Benign	0.72	T;T
Polyphen		0.046	B;.
Vest4		0.045
MutPred		0.63		Loss of helix (P = 0.1299);.;
MVP		0.095
MPC		0.078
ClinPred		0.098	T
GERP RS		2.7
Varity_R		0.055
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-46976851;