rs1730874

Positions:

• chr4-68316983-G-A
• chr4-68316983-G-T

Variant summary

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

The NM_001031732.4(YTHDC1):​c.1825-535C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 152,332 control chromosomes in the GnomAD database, including 75,291 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 0.99 (75291 hom., cov: 32)
• Consequence: YTHDC1 NM_001031732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383

Genes affected

YTHDC1 (HGNC:30626): (YTH N6-methyladenosine RNA binding protein C1) Enables N6-methyladenosine-containing RNA binding activity. Involved in mRNA export from nucleus; mRNA splice site selection; and regulation of gene expression. Located in nuclear speck and plasma membrane. [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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YTHDC1	NM_001031732.4	c.1825-535C>T		intron_variant		ENST00000344157.9
YTHDC1	NM_001330698.2	c.1849-535C>T		intron_variant
YTHDC1	NM_133370.4	c.1771-535C>T		intron_variant
YTHDC1	XM_005265708.4	c.1795-535C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YTHDC1	ENST00000344157.9	c.1825-535C>T		intron_variant		1	NM_001031732.4	P2
YTHDC1	ENST00000355665.7	c.1771-535C>T		intron_variant		1		A2
YTHDC1	ENST00000507529.1	c.96-535C>T		intron_variant		3
YTHDC1	ENST00000579690.5	c.1849-535C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.994 AC: 151331 AN: 152214 Hom.: 75233 Cov.: 32

Gnomad AFR AF: 0.981

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.996

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.994

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

GnomAD4 genome AF: 0.994 AC: 151448 AN: 152332 Hom.: 75291 Cov.: 32 AF XY: 0.995 AC XY: 74085 AN XY: 74492

Gnomad4 AFR AF: 0.981

Gnomad4 AMR AF: 0.996

Gnomad4 ASJ AF: 0.998

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.994

Alfa AF: 0.996 Hom.: 9367

Bravo AF: 0.994

Asia WGS AF: 0.999 AC: 3475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.71
DANN	Benign	0.15

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: rs1730874; hg19: chr4-69182701;