6-61800405-A-G

Variant names:

• chr6-61800405-A-G
• rs1743448
• NM_152688.4:c.811-67641T>C

Variant summary

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

The NM_152688.4(KHDRBS2):​c.811-67641T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,892 control chromosomes in the GnomAD database, including 32,039 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 0.64 (32039 hom., cov: 31)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604
• Publications: 4 publications found

Genes affected

KHDRBS2 (HGNC:18114): (KH RNA binding domain containing, signal transduction associated 2) Predicted to enable mRNA binding activity and poly(A) binding activity. Predicted to be involved in regulation of alternative mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152688.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHDRBS2	NM_152688.4	MANE Select	c.811-67641T>C		intron	N/A	NP_689901.2
	KHDRBS2	NM_001350622.2		c.861+16550T>C		intron	N/A	NP_001337551.1
	KHDRBS2	NR_146870.2		n.1088-67641T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHDRBS2	ENST00000281156.5	TSL:1 MANE Select	c.811-67641T>C		intron	N/A	ENSP00000281156.3
	KHDRBS2	ENST00000675091.1		n.811-67641T>C		intron	N/A	ENSP00000502245.1
	KHDRBS2	ENST00000718012.1		n.811-67641T>C		intron	N/A	ENSP00000520654.1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97440 AN: 151774 Hom.: 31991 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.642 AC: 97543 AN: 151892 Hom.: 32039 Cov.: 31 AF XY: 0.644 AC XY: 47791 AN XY: 74204

African (AFR) AF: 0.788 AC: 32712 AN: 41488

American (AMR) AF: 0.588 AC: 8960 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2248 AN: 3468

East Asian (EAS) AF: 0.526 AC: 2700 AN: 5132

South Asian (SAS) AF: 0.682 AC: 3276 AN: 4804

European-Finnish (FIN) AF: 0.630 AC: 6654 AN: 10566

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.576 AC: 39114 AN: 67896

Other (OTH) AF: 0.605 AC: 1275 AN: 2108

Alfa AF: 0.591 Hom.: 35886

Bravo AF: 0.642

Asia WGS AF: 0.667 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1743448; hg19: chr6-62510310;