6-46904916-A-G

Variant names:

• chr6-46904916-A-G
• rs1234123
• NM_001098518.2:c.102+1745T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098518.2(ADGRF5):​c.102+1745T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,652 control chromosomes in the GnomAD database, including 12,229 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (12229 hom., cov: 31)
• Consequence: ADGRF5 NM_001098518.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260

Genes affected

ADGRF5 (HGNC:19030): (adhesion G protein-coupled receptor F5) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and cell surface receptor signaling pathway. Predicted to act upstream of or within several processes, including glomerular filtration; pharyngeal arch artery morphogenesis; and surfactant homeostasis. Located in cell surface and cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ADGRF5-AS1 (HGNC:40864): (ADGRF5 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRF5	NM_001098518.2	c.102+1745T>C		intron_variant	Intron 2 of 20	ENST00000283296.12	NP_001091988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRF5	ENST00000283296.12	c.102+1745T>C		intron_variant	Intron 2 of 20	1	NM_001098518.2	ENSP00000283296.7
ADGRF5	ENST00000265417.7	c.102+1745T>C		intron_variant	Intron 2 of 20	1		ENSP00000265417.6
ADGRF5-AS1	ENST00000451135.1	n.109-343A>G		intron_variant	Intron 1 of 3	1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55045 AN: 151534 Hom.: 12230 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.363 AC: 55038 AN: 151652 Hom.: 12229 Cov.: 31 AF XY: 0.365 AC XY: 27058 AN XY: 74128

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.376

Alfa AF: 0.309 Hom.: 1019

Bravo AF: 0.337

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1234123; hg19: chr6-46872653;