1-201490271-G-A

Variant names:

• chr1-201490271-G-A
• rs504667
• NM_004078.3:c.186C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004078.3(CSRP1):​c.186C>T​(p.Tyr62Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 1,614,130 control chromosomes in the GnomAD database, including 241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (133 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (108 hom.)
• Consequence: CSRP1 NM_004078.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.46
• Publications: 2 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-201490271-G-A is Benign according to our data. Variant chr1-201490271-G-A is described in ClinVar as Benign. ClinVar VariationId is 775640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

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.186C>T	p.Tyr62Tyr	synonymous	Exon 3 of 6	NP_004069.1	A0A384P5K2
	CSRP1	NM_001193571.2		c.186C>T	p.Tyr62Tyr	synonymous	Exon 3 of 6	NP_001180500.1	P21291
	CSRP1	NM_001193572.2		c.186C>T	p.Tyr62Tyr	synonymous	Exon 3 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.186C>T	p.Tyr62Tyr	synonymous	Exon 3 of 6	ENSP00000345079.2	P21291
	CSRP1	ENST00000532313.5	TSL:1	n.184C>T		non_coding_transcript_exon	Exon 2 of 4
	CSRP1	ENST00000533402.5	TSL:1	n.2229C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3513 AN: 152136 Hom.: 131 Cov.: 32

Gnomad AFR AF: 0.0795

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00969

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0206

GnomAD2 exomes AF: 0.00629 AC: 1581 AN: 251436 AF XY: 0.00473

Gnomad AFR exome AF: 0.0822

Gnomad AMR exome AF: 0.00468

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000484

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00251 AC: 3664 AN: 1461876 Hom.: 108 Cov.: 30 AF XY: 0.00215 AC XY: 1567 AN XY: 727242

African (AFR) AF: 0.0841 AC: 2816 AN: 33476

American (AMR) AF: 0.00476 AC: 213 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00434 AC: 25 AN: 5766

European-Non Finnish (NFE) AF: 0.000236 AC: 262 AN: 1112004

Other (OTH) AF: 0.00527 AC: 318 AN: 60394

GnomAD4 genome AF: 0.0231 AC: 3517 AN: 152254 Hom.: 133 Cov.: 32 AF XY: 0.0219 AC XY: 1631 AN XY: 74438

African (AFR) AF: 0.0794 AC: 3298 AN: 41536

American (AMR) AF: 0.00961 AC: 147 AN: 15294

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

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68026

Other (OTH) AF: 0.0204 AC: 43 AN: 2112

Alfa AF: 0.0127 Hom.: 61

Bravo AF: 0.0269

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000593

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	-0.80
CADD	Benign	0.23
DANN	Benign	0.62
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs504667; hg19: chr1-201459399;