4-69934249-A-G

Variant names:

• chr4-69934249-A-G
• rs189052160
• NM_001890.2:c.84+5A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001890.2(CSN1S1):​c.84+5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000602 in 1,610,634 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (8 hom.)
• Consequence: CSN1S1 NM_001890.2 splice_region, intron
• Scores: Splicing: ADA: 0.00002064
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

Genes affected

CSN1S1 (HGNC:2445): (casein alpha s1) Predicted to be involved in response to dehydroepiandrosterone; response to estradiol; and response to steroid hormone. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 4-69934249-A-G is Benign according to our data. Variant chr4-69934249-A-G is described in ClinVar as [Benign]. Clinvar id is 782694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSN1S1	NM_001890.2	c.84+5A>G		splice_region_variant, intron_variant	Intron 3 of 15	ENST00000246891.9	NP_001881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSN1S1	ENST00000246891.9	c.84+5A>G		splice_region_variant, intron_variant	Intron 3 of 15	1	NM_001890.2	ENSP00000246891.4
CSN1S1	ENST00000507772.5	c.84+5A>G		splice_region_variant, intron_variant	Intron 2 of 13	5		ENSP00000427490.1
CSN1S1	ENST00000507763.5	c.84+5A>G		splice_region_variant, intron_variant	Intron 2 of 13	5		ENSP00000422611.1
CSN1S1	ENST00000505782.5	c.84+5A>G		splice_region_variant, intron_variant	Intron 2 of 12	5		ENSP00000426684.1

Frequencies

GnomAD3 genomes AF: 0.00176 AC: 268 AN: 152052 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00191 AC: 472 AN: 247506 AF XY: 0.00153

Gnomad AFR exome AF: 0.000260

Gnomad AMR exome AF: 0.0135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00167

GnomAD4 exome AF: 0.000481 AC: 701 AN: 1458464 Hom.: 8 Cov.: 29 AF XY: 0.000411 AC XY: 298 AN XY: 725636

African (AFR) AF: 0.000180 AC: 6 AN: 33336

American (AMR) AF: 0.0149 AC: 660 AN: 44226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39550

South Asian (SAS) AF: 0.00 AC: 0 AN: 85984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000541 AC: 6 AN: 1110002

Other (OTH) AF: 0.000482 AC: 29 AN: 60214

GnomAD4 genome AF: 0.00176 AC: 268 AN: 152170 Hom.: 4 Cov.: 32 AF XY: 0.00235 AC XY: 175 AN XY: 74392

African (AFR) AF: 0.000193 AC: 8 AN: 41550

American (AMR) AF: 0.0167 AC: 254 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67998

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000571 Hom.: 2

Bravo AF: 0.00272

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.60
PhyloP100		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.030		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: rs189052160; hg19: chr4-70799967;