rs10406920

Variant names:

• chr19-17278839-C-T
• rs10406920
• NM_014173.4:c.787-6C>T

Variant summary

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

The NM_014173.4(BABAM1):​c.787-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,608,172 control chromosomes in the GnomAD database, including 25,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2410 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23098 hom.)
• Consequence: BABAM1 NM_014173.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002312
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798
• Publications: 20 publications found

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]

ENSG00000269307 (HGNC:):

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.787-6C>T		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.787-6C>T		splice_region_variant, intron_variant	Intron 8 of 8		NP_001028721.1
BABAM1	NM_001288756.2	c.787-6C>T		splice_region_variant, intron_variant	Intron 8 of 8		NP_001275685.1
BABAM1	NM_001288757.2	c.562-6C>T		splice_region_variant, intron_variant	Intron 5 of 5		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6	c.787-6C>T		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_014173.4	ENSP00000471605.1
ENSG00000269307	ENST00000596542.1	n.*400+1930C>T		intron_variant	Intron 7 of 9	2		ENSP00000469159.2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26092 AN: 152062 Hom.: 2411 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.159

GnomAD2 exomes AF: 0.147 AC: 35422 AN: 240154 AF XY: 0.150

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.0790

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.000562

Gnomad FIN exome AF: 0.240

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.173 AC: 252053 AN: 1455992 Hom.: 23098 Cov.: 32 AF XY: 0.172 AC XY: 124619 AN XY: 723778

African (AFR) AF: 0.182 AC: 6095 AN: 33406

American (AMR) AF: 0.0825 AC: 3645 AN: 44206

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 4456 AN: 25938

East Asian (EAS) AF: 0.000505 AC: 20 AN: 39640

South Asian (SAS) AF: 0.118 AC: 10079 AN: 85316

European-Finnish (FIN) AF: 0.237 AC: 12527 AN: 52766

Middle Eastern (MID) AF: 0.103 AC: 595 AN: 5754

European-Non Finnish (NFE) AF: 0.185 AC: 204944 AN: 1108776

Other (OTH) AF: 0.161 AC: 9692 AN: 60190

GnomAD4 genome AF: 0.171 AC: 26089 AN: 152180 Hom.: 2410 Cov.: 32 AF XY: 0.170 AC XY: 12611 AN XY: 74398

African (AFR) AF: 0.185 AC: 7666 AN: 41512

American (AMR) AF: 0.107 AC: 1629 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.108 AC: 519 AN: 4820

European-Finnish (FIN) AF: 0.238 AC: 2519 AN: 10590

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12715 AN: 68000

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.175 Hom.: 2398

Bravo AF: 0.161

Asia WGS AF: 0.0570 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.38
PhyloP100		0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0020
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: rs10406920; hg19: chr19-17389648; COSMIC: COSV63921267; COSMIC: COSV63921267;