chr10-96192018-G-A

Variant names:

• chr10-96192018-G-A
• rs931320409
• NM_013314.4:c.1326C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_013314.4(BLNK):​c.1326C>T​(p.Asn442Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: BLNK NM_013314.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.28
• Publications: 0 publications found

Genes affected

BLNK (HGNC:14211): (B cell linker) This gene encodes a cytoplasmic linker or adaptor protein that plays a critical role in B cell development. This protein bridges B cell receptor-associated kinase activation with downstream signaling pathways, thereby affecting various biological functions. The phosphorylation of five tyrosine residues is necessary for this protein to nucleate distinct signaling effectors following B cell receptor activation. Mutations in this gene cause hypoglobulinemia and absent B cells, a disease in which the pro- to pre-B-cell transition is developmentally blocked. Deficiency in this protein has also been shown in some cases of pre-B acute lymphoblastic leukemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]

ZNF518A (HGNC:29009): (zinc finger protein 518A) The protein encoded by this gene is a member of the krueppel C2H2-type zinc finger protein family. The encoded protein contains five zinc fingers and is likely a nuclear transcriptional regulator. Numerous transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.096).
• BP6: Variant 10-96192018-G-A is Benign according to our data. Variant chr10-96192018-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3649167.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.28 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013314.4. 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
	BLNK	NM_013314.4	MANE Select	c.1326C>T	p.Asn442Asn	synonymous	Exon 17 of 17	NP_037446.1	Q8WV28-1
	BLNK	NM_001114094.2		c.1257C>T	p.Asn419Asn	synonymous	Exon 16 of 16	NP_001107566.1	Q8WV28-2
	BLNK	NM_001258440.2		c.1170C>T	p.Asn390Asn	synonymous	Exon 16 of 16	NP_001245369.1	Q8WV28-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLNK	ENST00000224337.10	TSL:1 MANE Select	c.1326C>T	p.Asn442Asn	synonymous	Exon 17 of 17	ENSP00000224337.6	Q8WV28-1
	BLNK	ENST00000371176.7	TSL:1	c.1257C>T	p.Asn419Asn	synonymous	Exon 16 of 16	ENSP00000360218.2	Q8WV28-2
	BLNK	ENST00000413476.6	TSL:1	c.1170C>T	p.Asn390Asn	synonymous	Exon 16 of 16	ENSP00000397487.2	Q8WV28-3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152052 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74406

African (AFR) AF: 0.00 AC: 0 AN: 41518

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2112

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Agammaglobulinemia 4, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.4
DANN	Benign	0.81
PhyloP100		2.3

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: rs931320409; hg19: chr10-97951774;