rs4740033

Variant names:

• chr8-84850368-A-C
• rs4740033
• NM_173848.7:c.413+341A>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.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
• Publications: 8 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]

ENSG00000293727 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173848.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALYL	NM_173848.7	MANE Select	c.413+341A>C		intron	N/A	NP_776247.3
	RALYL	NM_001413323.1		c.518+341A>C		intron	N/A	NP_001400252.1
	RALYL	NM_001413301.1		c.506+341A>C		intron	N/A	NP_001400230.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALYL	ENST00000521268.6	TSL:1 MANE Select	c.413+341A>C		intron	N/A	ENSP00000430367.1	Q86SE5-1
	RALYL	ENST00000517638.5	TSL:1	c.452+341A>C		intron	N/A	ENSP00000430128.1	Q86SE5-3
	RALYL	ENST00000521695.5	TSL:2	c.413+341A>C		intron	N/A	ENSP00000428667.1	Q86SE5-1

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

African (AFR) AF: 0.0949 AC: 3943 AN: 41546

American (AMR) AF: 0.408 AC: 6237 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1624 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1396 AN: 5182

South Asian (SAS) AF: 0.545 AC: 2627 AN: 4822

European-Finnish (FIN) AF: 0.451 AC: 4750 AN: 10542

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32915 AN: 67940

Other (OTH) AF: 0.400 AC: 844 AN: 2112

Alfa AF: 0.448 Hom.: 47418

Bravo AF: 0.342

Asia WGS AF: 0.394 AC: 1368 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.75
PhyloP100		0.83
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: rs4740033; hg19: chr8-85762603;