1-201488879-C-T

Variant names:

• chr1-201488879-C-T
• rs61738281
• NM_004078.3:c.387G>A

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_004078.3(CSRP1):​c.387G>A​(p.Ala129Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,614,080 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (50 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (41 hom.)
• Consequence: CSRP1 NM_004078.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.61
• 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=-0.57).
• BP6: Variant 1-201488879-C-T is Benign according to our data. Variant chr1-201488879-C-T is described in ClinVar as Benign. ClinVar VariationId is 711842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.61 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2141/152310) while in subpopulation AFR AF = 0.0474 (1969/41548). AF 95% confidence interval is 0.0456. There are 50 homozygotes in GnomAd4. There are 1004 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 50 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.387G>A	p.Ala129Ala	synonymous	Exon 4 of 6	NP_004069.1	A0A384P5K2
	CSRP1	NM_001193571.2		c.387G>A	p.Ala129Ala	synonymous	Exon 4 of 6	NP_001180500.1	P21291
	CSRP1	NM_001193572.2		c.387G>A	p.Ala129Ala	synonymous	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.387G>A	p.Ala129Ala	synonymous	Exon 4 of 6	ENSP00000345079.2	P21291
	CSRP1	ENST00000532313.5	TSL:1	n.385G>A		non_coding_transcript_exon	Exon 3 of 4
	CSRP1	ENST00000533402.5	TSL:1	n.3621G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2141 AN: 152192 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00403 AC: 1014 AN: 251312 AF XY: 0.00294

Gnomad AFR exome AF: 0.0504

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00156 AC: 2277 AN: 1461770 Hom.: 41 Cov.: 30 AF XY: 0.00145 AC XY: 1054 AN XY: 727198

African (AFR) AF: 0.0462 AC: 1546 AN: 33478

American (AMR) AF: 0.00356 AC: 159 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.00285 AC: 246 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.0000908 AC: 101 AN: 1111958

Other (OTH) AF: 0.00349 AC: 211 AN: 60380

GnomAD4 genome AF: 0.0141 AC: 2141 AN: 152310 Hom.: 50 Cov.: 32 AF XY: 0.0135 AC XY: 1004 AN XY: 74476

African (AFR) AF: 0.0474 AC: 1969 AN: 41548

American (AMR) AF: 0.00758 AC: 116 AN: 15300

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

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

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68034

Other (OTH) AF: 0.0104 AC: 22 AN: 2110

Alfa AF: 0.00608 Hom.: 12

Bravo AF: 0.0162

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000296

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	-0.57
CADD	Benign	1.5
DANN	Benign	0.62
PhyloP100		-5.6
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs61738281; hg19: chr1-201458007;