19-48638275-T-C

Variant names:

• chr19-48638275-T-C
• rs3848543
• NM_001217.5:c.962-131A>G

Variant summary

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

The NM_001217.5(CA11):​c.962-131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,174,836 control chromosomes in the GnomAD database, including 422,040 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 0.82 (50887 hom., cov: 24)
  • Exomes 𝑓: 0.85 (371153 hom.)
• Consequence: CA11 NM_001217.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 15 publications found

Genes affected

CA11 (HGNC:1370): (carbonic anhydrase 11) Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. CA XI is likely a secreted protein, however, radical changes at active site residues completely conserved in CA isozymes with catalytic activity, make it unlikely that it has carbonic anhydrase activity. It shares properties in common with two other acatalytic CA isoforms, CA VIII and CA X. CA XI is most abundantly expressed in brain, and may play a general role in the central nervous system. [provided by RefSeq, Jul 2008]

SEC1P (HGNC:):

SEC1P (HGNC:44149): (secretory blood group 1, pseudogene) Predicted to enable galactoside 2-alpha-L-fucosyltransferase activity. Predicted to act upstream of or within protein glycosylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001217.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA11	NM_001217.5	MANE Select	c.962-131A>G		intron	N/A	NP_001208.2
	CA11	NR_136241.2		n.2129A>G		non_coding_transcript_exon	Exon 8 of 9
	SEC1P	NR_004401.2		n.108+129T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA11	ENST00000084798.9	TSL:1 MANE Select	c.962-131A>G		intron	N/A	ENSP00000084798.3
	SEC1P	ENST00000474419.5	TSL:1	n.76+129T>C		intron	N/A
	SEC1P	ENST00000483163.1	TSL:1	n.76+129T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.822 AC: 123303 AN: 149982 Hom.: 50854 Cov.: 24

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.839

GnomAD2 exomes AF: 0.830 AC: 11322 AN: 13648 AF XY: 0.833

Gnomad AFR exome AF: 0.788

Gnomad AMR exome AF: 0.827

Gnomad ASJ exome AF: 0.814

Gnomad EAS exome AF: 0.680

Gnomad FIN exome AF: 0.812

Gnomad NFE exome AF: 0.861

Gnomad OTH exome AF: 0.872

GnomAD4 exome AF: 0.849 AC: 870220 AN: 1024736 Hom.: 371153 Cov.: 30 AF XY: 0.850 AC XY: 411943 AN XY: 484868

African (AFR) AF: 0.782 AC: 16761 AN: 21424

American (AMR) AF: 0.817 AC: 5590 AN: 6842

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 9402 AN: 11184

East Asian (EAS) AF: 0.541 AC: 12294 AN: 22742

South Asian (SAS) AF: 0.808 AC: 20402 AN: 25242

European-Finnish (FIN) AF: 0.806 AC: 17877 AN: 22170

Middle Eastern (MID) AF: 0.871 AC: 2322 AN: 2666

European-Non Finnish (NFE) AF: 0.862 AC: 752825 AN: 873700

Other (OTH) AF: 0.845 AC: 32747 AN: 38766

GnomAD4 genome AF: 0.822 AC: 123396 AN: 150100 Hom.: 50887 Cov.: 24 AF XY: 0.819 AC XY: 59939 AN XY: 73218

African (AFR) AF: 0.792 AC: 32293 AN: 40774

American (AMR) AF: 0.827 AC: 12488 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2960 AN: 3462

East Asian (EAS) AF: 0.629 AC: 3129 AN: 4974

South Asian (SAS) AF: 0.794 AC: 3735 AN: 4706

European-Finnish (FIN) AF: 0.821 AC: 8373 AN: 10204

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 57668 AN: 67596

Other (OTH) AF: 0.840 AC: 1753 AN: 2086

Alfa AF: 0.822 Hom.: 7117

Bravo AF: 0.823

Asia WGS AF: 0.707 AC: 2455 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.72
PhyloP100		0.074
Mutation Taster		=100/0	polymorphism (auto)

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: rs3848543; hg19: chr19-49141532; COSMIC: COSV50033660; COSMIC: COSV50033660;