rs142508597

Variant names:

• chr1-201488934-T-A
• rs142508597
• NM_004078.3:c.332A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-201488934-T-A
• chr1-201488934-T-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_004078.3(CSRP1):​c.332A>T​(p.Gln111Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000397 in 1,614,026 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (2 hom.)
• Consequence: CSRP1 NM_004078.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.03
• Publications: 0 publications found

Genes affected

CSRP1 (HGNC:2469): (cysteine and glycine rich protein 1) This gene encodes a member of the cysteine-rich protein (CSRP) family. This gene family includes a group of LIM domain proteins, which may be involved in regulatory processes important for development and cellular differentiation. The LIM/double zinc-finger motif found in this gene product occurs in proteins with critical functions in gene regulation, cell growth, and somatic differentiation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2010]

CSRP1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21749341).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004078.3. 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
	CSRP1	NM_004078.3	MANE Select	c.332A>T	p.Gln111Leu	missense	Exon 4 of 6	NP_004069.1	A0A384P5K2
	CSRP1	NM_001193571.2		c.332A>T	p.Gln111Leu	missense	Exon 4 of 6	NP_001180500.1	P21291
	CSRP1	NM_001193572.2		c.332A>T	p.Gln111Leu	missense	Exon 4 of 6	NP_001180501.1	A0A384P5K2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSRP1	ENST00000340006.7	TSL:1 MANE Select	c.332A>T	p.Gln111Leu	missense	Exon 4 of 6	ENSP00000345079.2	P21291
	CSRP1	ENST00000532313.5	TSL:1	n.330A>T		non_coding_transcript_exon	Exon 3 of 4
	CSRP1	ENST00000533402.5	TSL:1	n.3566A>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000367

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000107 AC: 27 AN: 251408 AF XY: 0.0000957

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000418 AC: 611 AN: 1461846 Hom.: 2 Cov.: 30 AF XY: 0.000402 AC XY: 292 AN XY: 727228

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000535 AC: 595 AN: 1111990

Other (OTH) AF: 0.000182 AC: 11 AN: 60392

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74348

African (AFR) AF: 0.0000483 AC: 2 AN: 41436

American (AMR) AF: 0.000131 AC: 2 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.000193

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.0
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.15
Sift	Benign	0.11	T
Sift4G	Benign	0.29	T
Polyphen		0.039	B
Vest4		0.74
MVP		0.63
MPC		0.21
ClinPred		0.16	T
GERP RS		5.5
Varity_R		0.32
gMVP		0.53
Mutation Taster		=21/79	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs142508597; hg19: chr1-201458062;