chr6-46904916-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098518.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRF5	NM_001098518.2	MANE Select	c.102+1745T>C		intron	N/A	NP_001091988.1
	ADGRF5	NM_015234.5		c.102+1745T>C		intron	N/A	NP_056049.4
	ADGRF5-AS1	NR_110658.1		n.109-343A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRF5	ENST00000283296.12	TSL:1 MANE Select	c.102+1745T>C		intron	N/A	ENSP00000283296.7
	ADGRF5	ENST00000265417.7	TSL:1	c.102+1745T>C		intron	N/A	ENSP00000265417.6
	ADGRF5-AS1	ENST00000451135.1	TSL:1	n.109-343A>G		intron	N/A

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

African (AFR) AF: 0.111 AC: 4592 AN: 41318

American (AMR) AF: 0.338 AC: 5155 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1388 AN: 3464

East Asian (EAS) AF: 0.483 AC: 2479 AN: 5128

South Asian (SAS) AF: 0.239 AC: 1151 AN: 4810

European-Finnish (FIN) AF: 0.577 AC: 6084 AN: 10548

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.484 AC: 32812 AN: 67820

Other (OTH) AF: 0.376 AC: 795 AN: 2112

Alfa AF: 0.297 Hom.: 1025

Bravo AF: 0.337

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.74
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1234123; hg19: chr6-46872653;