rs6937603

Variant names:

• chr6-42173588-A-G
• rs6937603
• NM_001384910.1:c.-26A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-42173588-A-G
• chr6-42173588-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001384910.1(GUCA1A):​c.-26A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,592,506 control chromosomes in the GnomAD database, including 8,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (4430 hom., cov: 33)
  • Exomes 𝑓: 0.015 (3958 hom.)
• Consequence: GUCA1A NM_001384910.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.226
• Publications: 3 publications found

Genes affected

GUCA1A (HGNC:4678): (guanylate cyclase activator 1A) This gene encodes an enzyme that plays a role in the recovery of retinal photoreceptors from photobleaching. This enzyme promotes the activity of retinal guanylyl cyclase-1 (GC1) at low calcium concentrations and inhibits GC1 at high calcium concentrations. Mutations in this gene can cause cone dystrophy 3 and code-rod dystrophy 14. provided by RefSeq, Jul 2020]

GUCA1ANB-GUCA1A (HGNC:56129): (GUCA1ANB-GUCA1A readthrough) This locus represents naturally occurring readthrough transcription between the neighboring GUCA1ANB (GUCA1A neighbor) and GUCA1A (guanylate cyclase activator 1A) genes on chromosome 6. The readthrough transcript encodes the same protein as GUCA1A. [provided by RefSeq, Jul 2020]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-42173588-A-G is Benign according to our data. Variant chr6-42173588-A-G is described in ClinVar as Benign. ClinVar VariationId is 356691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384910.1. 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
	GUCA1A	NM_001384910.1	MANE Select	c.-26A>G		5_prime_UTR	Exon 1 of 4	NP_001371839.1	P43080
	GUCA1ANB-GUCA1A	NM_000409.5		c.-26A>G		5_prime_UTR	Exon 3 of 6	NP_000400.2
	GUCA1ANB-GUCA1A	NM_001319061.2		c.-26A>G		5_prime_UTR	Exon 3 of 6	NP_001305990.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCA1A	ENST00000372958.2	TSL:1 MANE Select	c.-26A>G		5_prime_UTR	Exon 1 of 4	ENSP00000362049.1	P43080
	GUCA1ANB-GUCA1A	ENST00000654459.1		c.-26A>G		5_prime_UTR	Exon 2 of 5	ENSP00000499539.1
	GUCA1ANB-GUCA1A	ENST00000703265.1		n.*210A>G		non_coding_transcript_exon	Exon 3 of 4	ENSP00000515250.1	A6PVH5

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20274 AN: 152134 Hom.: 4410 Cov.: 33

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0606

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00328

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.0361 AC: 9069 AN: 250898 AF XY: 0.0269

Gnomad AFR exome AF: 0.460

Gnomad AMR exome AF: 0.0301

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.000598

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.00299

Gnomad OTH exome AF: 0.0211

GnomAD4 exome AF: 0.0151 AC: 21749 AN: 1440254 Hom.: 3958 Cov.: 28 AF XY: 0.0132 AC XY: 9469 AN XY: 717862

African (AFR) AF: 0.470 AC: 15509 AN: 32988

American (AMR) AF: 0.0340 AC: 1520 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00276 AC: 72 AN: 26056

East Asian (EAS) AF: 0.000429 AC: 17 AN: 39604

South Asian (SAS) AF: 0.00181 AC: 155 AN: 85816

European-Finnish (FIN) AF: 0.0000752 AC: 4 AN: 53204

Middle Eastern (MID) AF: 0.0468 AC: 235 AN: 5026

European-Non Finnish (NFE) AF: 0.00192 AC: 2103 AN: 1093246

Other (OTH) AF: 0.0358 AC: 2134 AN: 59628

GnomAD4 genome AF: 0.134 AC: 20341 AN: 152252 Hom.: 4430 Cov.: 33 AF XY: 0.129 AC XY: 9618 AN XY: 74466

African (AFR) AF: 0.456 AC: 18912 AN: 41482

American (AMR) AF: 0.0605 AC: 926 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.00328 AC: 223 AN: 68030

Other (OTH) AF: 0.110 AC: 232 AN: 2116

Alfa AF: 0.0467 Hom.: 2913

Bravo AF: 0.152

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cone dystrophy 3 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.45
PhyloP100		-0.23
PromoterAI		-0.036	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6937603; hg19: chr6-42141326;