1-84555086-G-A

Variant names:

• chr1-84555086-G-A
• rs138861244
• NM_004388.3:c.1071C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004388.3(CTBS):​c.1071C>T​(p.Asn357Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,613,946 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (68 hom.)
• Consequence: CTBS NM_004388.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.589
• Publications: 2 publications found

Genes affected

CTBS (HGNC:2496): (chitobiase) Chitobiase is a lysosomal glycosidase involved in degradation of asparagine-linked oligosaccharides on glycoproteins (Aronson and Kuranda, 1989 [PubMed 2531691]).[supplied by OMIM, Nov 2010]

SPATA1 (HGNC:14682): (spermatogenesis associated 1)

ENSG00000285851 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-84555086-G-A is Benign according to our data. Variant chr1-84555086-G-A is described in ClinVar as Benign. ClinVar VariationId is 718265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.589 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00338 (515/152214) while in subpopulation SAS AF = 0.0255 (123/4818). AF 95% confidence interval is 0.0219. There are 7 homozygotes in GnomAd4. There are 273 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004388.3. 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
	CTBS	NM_004388.3	MANE Select	c.1071C>T	p.Asn357Asn	synonymous	Exon 7 of 7	NP_004379.1	Q01459
	SPATA1	NM_001397487.1	MANE Select	c.1225-824G>A		intron	N/A	NP_001384416.1	A0A8V8TNU4
	SPATA1	NM_001310156.2		c.*1-824G>A		intron	N/A	NP_001297085.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBS	ENST00000370630.6	TSL:1 MANE Select	c.1071C>T	p.Asn357Asn	synonymous	Exon 7 of 7	ENSP00000359664.4	Q01459
	SPATA1	ENST00000699524.1	MANE Select	c.1225-824G>A		intron	N/A	ENSP00000514414.1	A0A8V8TNU4
	CTBS	ENST00000477677.5	TSL:1	n.927C>T		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.00337 AC: 512 AN: 152096 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00341

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0249

Gnomad FIN AF: 0.000567

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00393

Gnomad OTH AF: 0.00623

GnomAD2 exomes AF: 0.00653 AC: 1642 AN: 251396 AF XY: 0.00813

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.00953

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.00460

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00449 AC: 6565 AN: 1461732 Hom.: 68 Cov.: 31 AF XY: 0.00543 AC XY: 3951 AN XY: 727150

African (AFR) AF: 0.000388 AC: 13 AN: 33476

American (AMR) AF: 0.00248 AC: 111 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 226 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39680

South Asian (SAS) AF: 0.0279 AC: 2405 AN: 86244

European-Finnish (FIN) AF: 0.000655 AC: 35 AN: 53402

Middle Eastern (MID) AF: 0.0210 AC: 121 AN: 5766

European-Non Finnish (NFE) AF: 0.00300 AC: 3332 AN: 1111920

Other (OTH) AF: 0.00532 AC: 321 AN: 60388

GnomAD4 genome AF: 0.00338 AC: 515 AN: 152214 Hom.: 7 Cov.: 32 AF XY: 0.00367 AC XY: 273 AN XY: 74426

African (AFR) AF: 0.000337 AC: 14 AN: 41526

American (AMR) AF: 0.00340 AC: 52 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4818

European-Finnish (FIN) AF: 0.000567 AC: 6 AN: 10590

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00393 AC: 267 AN: 68016

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00423 Hom.: 1

Bravo AF: 0.00294

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.00671

EpiControl AF: 0.00765

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.0
DANN	Benign	0.76
PhyloP100		0.59
Mutation Taster		=98/2	polymorphism

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: rs138861244; hg19: chr1-85020769;