rs370101659

Variant names:

• chr9-137618754-C-A
• rs370101659
• ENST00000371417.4:n.125G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-137618754-C-A
• chr9-137618754-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000371417.4(ARRDC1-AS1):​n.125G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00538 in 152,292 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARRDC1-AS1 ENST00000371417.4 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650
• Publications: 0 publications found

Genes affected

ARRDC1-AS1 (HGNC:23395): (ARRDC1 antisense RNA 1) This transcribed locus is thought to be non-coding. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ENSG00000283411 (HGNC:):

EHMT1 (HGNC:24650): (euchromatic histone lysine methyltransferase 1) The protein encoded by this gene is a histone methyltransferase that methylates the lysine-9 position of histone H3. This action marks the genomic region packaged with these methylated histones for transcriptional repression. This protein may be involved in the silencing of MYC- and E2F-responsive genes and therefore could play a role in the G0/G1 cell cycle transition. Defects in this gene are a cause of chromosome 9q subtelomeric deletion syndrome (9q-syndrome, also known as Kleefstra syndrome). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

EHMT1 Gene-Disease associations (from GenCC):

• Kleefstra syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Kleefstra syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 9-137618754-C-A is Benign according to our data. Variant chr9-137618754-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1208625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00538 (819/152292) while in subpopulation AFR AF = 0.0176 (734/41592). AF 95% confidence interval is 0.0166. There are 8 homozygotes in GnomAd4. There are 363 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371417.4. 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
	ARRDC1-AS1	NR_122035.1		n.142G>T		non_coding_transcript_exon	Exon 1 of 3
	ARRDC1-AS1	NR_122036.1		n.-225G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARRDC1-AS1	ENST00000371417.4	TSL:1	n.125G>T		non_coding_transcript_exon	Exon 1 of 3
	ARRDC1-AS1	ENST00000496793.3	TSL:2	n.153G>T		non_coding_transcript_exon	Exon 1 of 2
	ARRDC1-AS1	ENST00000623970.1	TSL:5	n.78G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00533 AC: 811 AN: 152174 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00526

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 738 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 438

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 26

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24

East Asian (EAS) AF: 0.00 AC: 0 AN: 22

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 550

Other (OTH) AF: 0.00 AC: 0 AN: 50

GnomAD4 genome AF: 0.00538 AC: 819 AN: 152292 Hom.: 8 Cov.: 32 AF XY: 0.00487 AC XY: 363 AN XY: 74474

African (AFR) AF: 0.0176 AC: 734 AN: 41592

American (AMR) AF: 0.00385 AC: 59 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68002

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00813 Hom.: 4

Bravo AF: 0.00658

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.5
DANN	Benign	0.75
PhyloP100		0.065
PromoterAI		-0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs370101659; hg19: chr9-140513206;