chr6-42173531-G-A

Variant names:

• chr6-42173531-G-A
• rs9471793
• NM_001384910.1:c.-83G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001384910.1(GUCA1A):​c.-83G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,122,758 control chromosomes in the GnomAD database, including 10,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2819 hom., cov: 33)
  • Exomes 𝑓: 0.12 (7571 hom.)
• Consequence: GUCA1A NM_001384910.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.45
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-42173531-G-A is Benign according to our data. Variant chr6-42173531-G-A is described in ClinVar as Benign. ClinVar VariationId is 356690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 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.-83G>A		5_prime_UTR	Exon 1 of 4	NP_001371839.1	P43080
	GUCA1ANB-GUCA1A	NM_000409.5		c.-83G>A		5_prime_UTR	Exon 3 of 6	NP_000400.2
	GUCA1ANB-GUCA1A	NM_001319061.2		c.-83G>A		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.-83G>A		5_prime_UTR	Exon 1 of 4	ENSP00000362049.1	P43080
	GUCA1ANB-GUCA1A	ENST00000654459.1		c.-83G>A		5_prime_UTR	Exon 2 of 5	ENSP00000499539.1
	GUCA1ANB-GUCA1A	ENST00000703265.1		n.*153G>A		non_coding_transcript_exon	Exon 3 of 4	ENSP00000515250.1	A6PVH5

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25300 AN: 152092 Hom.: 2816 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0862

Gnomad FIN AF: 0.0857

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.116 AC: 112801 AN: 970548 Hom.: 7571 Cov.: 13 AF XY: 0.116 AC XY: 58238 AN XY: 503156

African (AFR) AF: 0.319 AC: 7668 AN: 24058

American (AMR) AF: 0.0701 AC: 3031 AN: 43232

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 2755 AN: 23048

East Asian (EAS) AF: 0.00260 AC: 97 AN: 37348

South Asian (SAS) AF: 0.0875 AC: 6642 AN: 75874

European-Finnish (FIN) AF: 0.0847 AC: 4111 AN: 48512

Middle Eastern (MID) AF: 0.172 AC: 555 AN: 3226

European-Non Finnish (NFE) AF: 0.123 AC: 82558 AN: 671192

Other (OTH) AF: 0.122 AC: 5384 AN: 44058

GnomAD4 genome AF: 0.166 AC: 25320 AN: 152210 Hom.: 2819 Cov.: 33 AF XY: 0.163 AC XY: 12103 AN XY: 74416

African (AFR) AF: 0.317 AC: 13146 AN: 41496

American (AMR) AF: 0.108 AC: 1646 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5182

South Asian (SAS) AF: 0.0860 AC: 415 AN: 4824

European-Finnish (FIN) AF: 0.0857 AC: 909 AN: 10606

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8360 AN: 68008

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.136 Hom.: 655

Bravo AF: 0.173

Asia WGS AF: 0.0580 AC: 204 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Cone dystrophy 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.94
DANN	Benign	0.49
PhyloP100		-1.5
PromoterAI		0.025	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: rs9471793; hg19: chr6-42141269; COSMIC: COSV50003914;