8-84890253-A-C

Variant names:

• chr8-84890253-A-C
• rs1427065
• NM_173848.7:c.858+2477A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173848.7(RALYL):​c.858+2477A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 152,138 control chromosomes in the GnomAD database, including 64,859 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 0.92 (64859 hom., cov: 30)
• Consequence: RALYL NM_173848.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 4 publications found

Genes affected

RALYL (HGNC:27036): (RALY RNA binding protein like) Enables identical protein binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RALYL	NM_173848.7	c.858+2477A>C		intron_variant	Intron 8 of 8	ENST00000521268.6	NP_776247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RALYL	ENST00000521268.6	c.858+2477A>C		intron_variant	Intron 8 of 8	1	NM_173848.7	ENSP00000430367.1

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140227 AN: 152020 Hom.: 64807 Cov.: 30

Gnomad AFR AF: 0.981

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.921

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

GnomAD4 genome AF: 0.922 AC: 140336 AN: 152138 Hom.: 64859 Cov.: 30 AF XY: 0.922 AC XY: 68575 AN XY: 74384

African (AFR) AF: 0.981 AC: 40707 AN: 41514

American (AMR) AF: 0.941 AC: 14363 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3036 AN: 3470

East Asian (EAS) AF: 0.959 AC: 4948 AN: 5160

South Asian (SAS) AF: 0.839 AC: 4039 AN: 4816

European-Finnish (FIN) AF: 0.914 AC: 9689 AN: 10598

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.890 AC: 60487 AN: 67990

Other (OTH) AF: 0.917 AC: 1940 AN: 2116

Alfa AF: 0.899 Hom.: 100982

Bravo AF: 0.931

Asia WGS AF: 0.909 AC: 3162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.77
PhyloP100		-0.053
Mutation Taster		=100/0	polymorphism (auto)

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: rs1427065; hg19: chr8-85802488;