chr19-17276776-G-A

Position:

• chr19-17276776-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014173.4(BABAM1):​c.700-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 1,570,410 control chromosomes in the GnomAD database, including 244 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 0.023 (135 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (109 hom.)
• Consequence: BABAM1 NM_014173.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177

Genes affected

BABAM1 (HGNC:25008): (BRISC and BRCA1 A complex member 1) Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; positive regulation of DNA repair; and protein K63-linked deubiquitination. Located in cytosol and nuclear body. Part of BRCA1-A complex and BRISC complex. [provided by Alliance of Genome Resources, Apr 2022]

USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BABAM1	NM_014173.4	c.700-47G>A		intron_variant		ENST00000598188.6
BABAM1	NM_001033549.3	c.700-47G>A		intron_variant
BABAM1	NM_001288756.2	c.700-47G>A		intron_variant
BABAM1	NM_001288757.2	c.475-47G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BABAM1	ENST00000598188.6	c.700-47G>A		intron_variant		1	NM_014173.4	P1

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3512 AN: 152178 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.00547 AC: 1026 AN: 187706 Hom.: 38 AF XY: 0.00440 AC XY: 443 AN XY: 100758

Gnomad AFR exome AF: 0.0815

Gnomad AMR exome AF: 0.00466

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000739

Gnomad SAS exome AF: 0.0000807

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000252

Gnomad OTH exome AF: 0.00141

GnomAD4 exome AF: 0.00243 AC: 3447 AN: 1418114 Hom.: 109 Cov.: 31 AF XY: 0.00208 AC XY: 1457 AN XY: 702076

Gnomad4 AFR exome AF: 0.0834

Gnomad4 AMR exome AF: 0.00493

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000266

Gnomad4 SAS exome AF: 0.000136

Gnomad4 FIN exome AF: 0.0000196

Gnomad4 NFE exome AF: 0.000166

Gnomad4 OTH exome AF: 0.00532

GnomAD4 genome AF: 0.0231 AC: 3517 AN: 152296 Hom.: 135 Cov.: 32 AF XY: 0.0222 AC XY: 1653 AN XY: 74478

Gnomad4 AFR AF: 0.0797

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00525 Hom.: 29

Bravo AF: 0.0252

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs10416551; hg19: chr19-17387585;