chr5-138753949-T-C

Variant names:

• chr5-138753949-T-C
• rs116214280
• NM_001903.5:c.-3+439T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001323983.1(CTNNA1):​c.-152T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00688 in 152,260 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (13 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTNNA1 NM_001323983.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.0960
• Publications: 0 publications found

Genes affected

CTNNA1 (HGNC:2509): (catenin alpha 1) This gene encodes a member of the catenin family of proteins that play an important role in cell adhesion process by connecting cadherins located on the plasma membrane to the actin filaments inside the cell. The encoded mechanosensing protein contains three vinculin homology domains and undergoes conformational changes in response to cytoskeletal tension, resulting in the reconfiguration of cadherin-actin filament connections. Certain mutations in this gene cause butterfly-shaped pigment dystrophy. [provided by RefSeq, May 2016]

CTNNA1-AS1 (HGNC:55535): (CTNNA1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-138753949-T-C is Benign according to our data. Variant chr5-138753949-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 223753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00688 (1047/152260) while in subpopulation AFR AF = 0.0234 (973/41578). AF 95% confidence interval is 0.0222. There are 13 homozygotes in GnomAd4. There are 497 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1047 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323983.1. 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
	CTNNA1	NM_001903.5	MANE Select	c.-3+439T>C		intron	N/A	NP_001894.2	A0A384MDY0
	CTNNA1	NM_001323983.1		c.-152T>C		5_prime_UTR	Exon 1 of 18	NP_001310912.1	A0A384MDY0
	CTNNA1	NM_001323982.2		c.-473+439T>C		intron	N/A	NP_001310911.1	P35221-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA1	ENST00000302763.12	TSL:1 MANE Select	c.-3+439T>C		intron	N/A	ENSP00000304669.7	P35221-1
	CTNNA1	ENST00000889709.1		c.-337T>C		5_prime_UTR	Exon 1 of 19	ENSP00000559768.1
	CTNNA1	ENST00000889710.1		c.-304T>C		5_prime_UTR	Exon 1 of 19	ENSP00000559769.1

Frequencies

GnomAD3 genomes AF: 0.00687 AC: 1045 AN: 152144 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00622

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 296 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 146

African (AFR) AF: 0.00 AC: 0 AN: 24

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14

East Asian (EAS) AF: 0.00 AC: 0 AN: 16

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 202

Other (OTH) AF: 0.00 AC: 0 AN: 24

GnomAD4 genome AF: 0.00688 AC: 1047 AN: 152260 Hom.: 13 Cov.: 32 AF XY: 0.00668 AC XY: 497 AN XY: 74454

African (AFR) AF: 0.0234 AC: 973 AN: 41578

American (AMR) AF: 0.00366 AC: 56 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67994

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00467 Hom.: 0

Bravo AF: 0.00795

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Benign	0.61
PhyloP100		0.096
PromoterAI		0.0028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs116214280; hg19: chr5-138089638;