chr22-50199493-G-C

Variant names:

• chr22-50199493-G-C
• rs6712
• NM_001320485.2:c.*974G>C

Variant summary

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

The NM_001320485.2(TRABD):​c.*974G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 202,468 control chromosomes in the GnomAD database, including 1,217 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 0.097 (900 hom., cov: 34)
  • Exomes 𝑓: 0.10 (317 hom.)
• Consequence: TRABD NM_001320485.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38
• Publications: 15 publications found

Genes affected

TRABD (HGNC:28805): (TraB domain containing)

TRABD-AS1 (HGNC:56049): (TRABD antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320485.2. 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
	TRABD	NM_001320485.2	MANE Select	c.*974G>C		3_prime_UTR	Exon 10 of 10	NP_001307414.1	Q9H4I3-1
	TRABD	NM_001320484.2		c.*974G>C		3_prime_UTR	Exon 10 of 10	NP_001307413.1
	TRABD	NM_001320488.2		c.*365G>C		3_prime_UTR	Exon 11 of 11	NP_001307417.1	J3KPT4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRABD	ENST00000380909.9	TSL:5 MANE Select	c.*974G>C		3_prime_UTR	Exon 10 of 10	ENSP00000370295.4	Q9H4I3-1
	TRABD	ENST00000303434.8	TSL:1	c.*974G>C		3_prime_UTR	Exon 10 of 10	ENSP00000305664.4	Q9H4I3-1
	TRABD	ENST00000463233.1	TSL:1	n.2302G>C		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14753 AN: 152202 Hom.: 901 Cov.: 34

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0962

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.0311

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.0965

GnomAD4 exome AF: 0.101 AC: 5077 AN: 50148 Hom.: 317 Cov.: 0 AF XY: 0.102 AC XY: 2578 AN XY: 25184

African (AFR) AF: 0.0200 AC: 40 AN: 1996

American (AMR) AF: 0.0687 AC: 95 AN: 1382

Ashkenazi Jewish (ASJ) AF: 0.0690 AC: 150 AN: 2174

East Asian (EAS) AF: 0.0201 AC: 67 AN: 3334

South Asian (SAS) AF: 0.200 AC: 303 AN: 1518

European-Finnish (FIN) AF: 0.0978 AC: 220 AN: 2250

Middle Eastern (MID) AF: 0.111 AC: 32 AN: 288

European-Non Finnish (NFE) AF: 0.114 AC: 3805 AN: 33492

Other (OTH) AF: 0.0983 AC: 365 AN: 3714

GnomAD4 genome AF: 0.0968 AC: 14749 AN: 152320 Hom.: 900 Cov.: 34 AF XY: 0.0991 AC XY: 7378 AN XY: 74486

African (AFR) AF: 0.0237 AC: 987 AN: 41574

American (AMR) AF: 0.0960 AC: 1470 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0821 AC: 285 AN: 3472

East Asian (EAS) AF: 0.0310 AC: 161 AN: 5190

South Asian (SAS) AF: 0.214 AC: 1034 AN: 4828

European-Finnish (FIN) AF: 0.125 AC: 1330 AN: 10616

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9114 AN: 68012

Other (OTH) AF: 0.0969 AC: 205 AN: 2116

Alfa AF: 0.0637 Hom.: 82

Bravo AF: 0.0890

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.73
DANN	Benign	0.47
PhyloP100		-3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6712; hg19: chr22-50637922;