6-146656764-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_024694.4(ADGB):c.403-7T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00917 in 1,511,436 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0095 (82 hom.)
• Consequence: ADGB NM_024694.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00006450
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0380

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-146656764-T-C is Benign according to our data. Variant chr6-146656764-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2656976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGB	NM_024694.4	c.403-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000397944.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGB	ENST00000397944.8	c.403-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_024694.4	P4

Frequencies

GnomAD3 genomes AF: 0.00634 AC: 965 AN: 152194 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00955

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00734 AC: 956 AN: 130318 Hom.: 7 AF XY: 0.00798 AC XY: 539 AN XY: 67568

Gnomad AFR exome AF: 0.00207

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.00286

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00795

Gnomad FIN exome AF: 0.0157

Gnomad NFE exome AF: 0.00930

Gnomad OTH exome AF: 0.00719

GnomAD4 exome AF: 0.00949 AC: 12898 AN: 1359124 Hom.: 82 Cov.: 29 AF XY: 0.00956 AC XY: 6372 AN XY: 666566

Gnomad4 AFR exome AF: 0.00139

Gnomad4 AMR exome AF: 0.00205

Gnomad4 ASJ exome AF: 0.00417

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00955

Gnomad4 FIN exome AF: 0.0145

Gnomad4 NFE exome AF: 0.0102

Gnomad4 OTH exome AF: 0.00767

GnomAD4 genome AF: 0.00633 AC: 964 AN: 152312 Hom.: 5 Cov.: 32 AF XY: 0.00632 AC XY: 471 AN XY: 74480

Gnomad4 AFR AF: 0.00161

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00828

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.00955

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00735 Hom.: 1

Bravo AF: 0.00502

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

ADGB: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.4
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000064
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs76071490; hg19: chr6-146977900;