chr22-24547326-C-T

Variant names:

• chr22-24547326-C-T
• rs12170895
• NM_001284254.2:c.295-321G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001284254.2(GUCD1):​c.295-321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 311,472 control chromosomes in the GnomAD database, including 3,187 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1488 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1699 hom.)
• Consequence: GUCD1 NM_001284254.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 4 publications found

Genes affected

GUCD1 (HGNC:14237): (guanylyl cyclase domain containing 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284254.2. 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
	GUCD1	NM_001284254.2	MANE Select	c.295-321G>A		intron	N/A	NP_001271183.1	Q96NT3-2
	GUCD1	NM_001284251.2		c.463-321G>A		intron	N/A	NP_001271180.1	A0A087WVD9
	GUCD1	NM_001284252.2		c.463-321G>A		intron	N/A	NP_001271181.1	Q96NT3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCD1	ENST00000435822.6	TSL:1 MANE Select	c.295-321G>A		intron	N/A	ENSP00000405985.1	Q96NT3-2
	GUCD1	ENST00000621833.4	TSL:1	c.463-321G>A		intron	N/A	ENSP00000479370.1	A0A087WVD9
	GUCD1	ENST00000404664.7	TSL:2	c.463-321G>A		intron	N/A	ENSP00000384121.3	Q96NT3-3

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20809 AN: 151894 Hom.: 1486 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0614

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.136 AC: 21678 AN: 159460 Hom.: 1699 Cov.: 0 AF XY: 0.140 AC XY: 11862 AN XY: 84578

African (AFR) AF: 0.121 AC: 681 AN: 5650

American (AMR) AF: 0.167 AC: 1215 AN: 7284

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 716 AN: 4760

East Asian (EAS) AF: 0.0740 AC: 698 AN: 9432

South Asian (SAS) AF: 0.197 AC: 3985 AN: 20196

European-Finnish (FIN) AF: 0.120 AC: 880 AN: 7346

Middle Eastern (MID) AF: 0.139 AC: 88 AN: 634

European-Non Finnish (NFE) AF: 0.128 AC: 12196 AN: 95120

Other (OTH) AF: 0.135 AC: 1219 AN: 9038

GnomAD4 genome AF: 0.137 AC: 20814 AN: 152012 Hom.: 1488 Cov.: 32 AF XY: 0.140 AC XY: 10417 AN XY: 74314

African (AFR) AF: 0.128 AC: 5295 AN: 41462

American (AMR) AF: 0.174 AC: 2661 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3468

East Asian (EAS) AF: 0.0613 AC: 317 AN: 5168

South Asian (SAS) AF: 0.230 AC: 1108 AN: 4812

European-Finnish (FIN) AF: 0.123 AC: 1297 AN: 10562

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9077 AN: 67972

Other (OTH) AF: 0.137 AC: 288 AN: 2108

Alfa AF: 0.136 Hom.: 2470

Bravo AF: 0.136

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.66
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs12170895; hg19: chr22-24943294;