rs373734099

Variant names:

• chr4-69944874-G-A
• rs373734099
• NM_001890.2:c.427G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-69944874-G-A
• chr4-69944874-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001890.2(CSN1S1):​c.427G>A​(p.Ala143Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A143S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSN1S1 NM_001890.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.386
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09758443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSN1S1	NM_001890.2	c.427G>A	p.Ala143Thr	missense_variant	Exon 15 of 16	ENST00000246891.9	NP_001881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSN1S1	ENST00000246891.9	c.427G>A	p.Ala143Thr	missense_variant	Exon 15 of 16	1	NM_001890.2	ENSP00000246891.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460496 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726562

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111100

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.88
DEOGEN2	Benign	0.056	T;.;.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.74	T;T;T;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.098	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.;.;.;.
PhyloP100		0.39
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.21	N;N;N;N;N
REVEL	Benign	0.034
Sift	Benign	0.041	D;D;D;D;T
Sift4G	Benign	0.24	T;T;T;T;T
Polyphen		0.28	B;.;B;.;.
Vest4		0.27
MutPred		0.55		Gain of relative solvent accessibility (P = 0.09);.;.;.;.;
MVP		0.18
MPC		0.22
ClinPred		0.093	T
GERP RS		-0.55
Varity_R		0.040
gMVP		0.039

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: rs373734099; hg19: chr4-70810592;