rs1730872

Variant names:

• chr4-68323330-A-G
• rs1730872
• NM_001031732.4:c.1435-415T>C

Variant summary

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

The NM_001031732.4(YTHDC1):​c.1435-415T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,248 control chromosomes in the GnomAD database, including 51,127 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 0.82 (51127 hom., cov: 34)
• Consequence: YTHDC1 NM_001031732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219
• Publications: 3 publications found

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]

YTHDC1 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YTHDC1	NM_001031732.4	c.1435-415T>C		intron_variant	Intron 10 of 16	ENST00000344157.9	NP_001026902.1
YTHDC1	NM_001330698.2	c.1435-415T>C		intron_variant	Intron 10 of 16		NP_001317627.1
YTHDC1	NM_133370.4	c.1381-415T>C		intron_variant	Intron 9 of 15		NP_588611.2
YTHDC1	XM_005265708.4	c.1381-415T>C		intron_variant	Intron 9 of 15		XP_005265765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YTHDC1	ENST00000344157.9	c.1435-415T>C		intron_variant	Intron 10 of 16	1	NM_001031732.4	ENSP00000339245.4
YTHDC1	ENST00000355665.7	c.1381-415T>C		intron_variant	Intron 9 of 15	1		ENSP00000347888.3
YTHDC1	ENST00000579690.5	c.1435-415T>C		intron_variant	Intron 10 of 16	5		ENSP00000463982.1
YTHDC1	ENST00000506175.1	n.158-415T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124239 AN: 152130 Hom.: 51086 Cov.: 34

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.817 AC: 124334 AN: 152248 Hom.: 51127 Cov.: 34 AF XY: 0.822 AC XY: 61212 AN XY: 74434

African (AFR) AF: 0.776 AC: 32224 AN: 41530

American (AMR) AF: 0.721 AC: 11023 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2792 AN: 3468

East Asian (EAS) AF: 0.966 AC: 5010 AN: 5184

South Asian (SAS) AF: 0.899 AC: 4340 AN: 4826

European-Finnish (FIN) AF: 0.909 AC: 9649 AN: 10614

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56645 AN: 68014

Other (OTH) AF: 0.808 AC: 1705 AN: 2110

Alfa AF: 0.797 Hom.: 12768

Bravo AF: 0.797

Asia WGS AF: 0.914 AC: 3179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		0.22
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: rs1730872; hg19: chr4-69189048;