chr6-146805738-T-C

Variant names:

• chr6-146805738-T-C
• rs9390422
• NM_024694.4:c.4818+3727T>C

Variant summary

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

The NM_024694.4(ADGB):​c.4818+3727T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,002 control chromosomes in the GnomAD database, including 9,825 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 0.34 (9825 hom., cov: 31)
• Consequence: ADGB NM_024694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• Publications: 3 publications found

Genes affected

ADGB (HGNC:21212): (androglobin) Predicted to enable calcium-dependent cysteine-type endopeptidase activity; heme binding activity; and oxygen binding activity. Predicted to be involved in proteolysis. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024694.4. 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
	ADGB	NM_024694.4	MANE Select	c.4818+3727T>C		intron	N/A	NP_078970.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGB	ENST00000397944.8	TSL:5 MANE Select	c.4818+3727T>C		intron	N/A	ENSP00000381036.3	Q8N7X0-1
	ADGB	ENST00000493950.6	TSL:1	n.*5649+3727T>C		intron	N/A	ENSP00000430244.1	E5RGD1
	ADGB	ENST00000470716.3	TSL:4	c.*589T>C		3_prime_UTR	Exon 7 of 7	ENSP00000427779.2	E5RG76

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52040 AN: 151884 Hom.: 9826 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.337

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.342 AC: 52046 AN: 152002 Hom.: 9825 Cov.: 31 AF XY: 0.342 AC XY: 25428 AN XY: 74296

African (AFR) AF: 0.200 AC: 8281 AN: 41502

American (AMR) AF: 0.445 AC: 6811 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1118 AN: 3464

East Asian (EAS) AF: 0.672 AC: 3453 AN: 5136

South Asian (SAS) AF: 0.396 AC: 1906 AN: 4812

European-Finnish (FIN) AF: 0.306 AC: 3236 AN: 10564

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26091 AN: 67918

Other (OTH) AF: 0.336 AC: 710 AN: 2112

Alfa AF: 0.376 Hom.: 46499

Bravo AF: 0.348

Asia WGS AF: 0.463 AC: 1607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.66
PhyloP100		0.36
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: rs9390422; hg19: chr6-147126874; COSMIC: COSV58847574; COSMIC: COSV58847574;