rs4740033

chr8-84850368-A-C

Variant summary

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

The NM_173848.7(RALYL):c.413+341A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,086 control chromosomes in the GnomAD database, including 12,283 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 (12283 hom., cov: 32)
• Consequence: RALYL NM_173848.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RALYL	NM_173848.7	c.413+341A>C		intron_variant		ENST00000521268.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RALYL	ENST00000521268.6	c.413+341A>C		intron_variant		1	NM_173848.7	P1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54889 AN: 151968 Hom.: 12289 Cov.: 32

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.361 AC: 54875 AN: 152086 Hom.: 12283 Cov.: 32 AF XY: 0.363 AC XY: 26972 AN XY: 74356

Gnomad4 AFR AF: 0.0949

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.400

Alfa AF: 0.467 Hom.: 34315

Bravo AF: 0.342

Asia WGS AF: 0.394 AC: 1368 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.5
Dann	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs4740033; hg19: chr8-85762603;